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Stieglitz J. Contemporary small-scale subsistence populations offer unique insights into human musculoskeletal health and aging. SCIENCE ADVANCES 2024; 10:eadq1039. [PMID: 39514654 PMCID: PMC11804946 DOI: 10.1126/sciadv.adq1039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 10/03/2024] [Indexed: 11/16/2024]
Abstract
Human foragers avoid noncommunicable diseases that are leading causes of mortality, partly because physically active lifestyles promote healthy aging. High activity levels also promote tissue damage accumulation from wear-and-tear, increase risk of injury and disability which compromise productivity, and reduce energetic investments in somatic maintenance given constrained energy expenditure. Constraints intensify when nutrient supply is limited and surplus energy is directed toward pathogen defense and reproduction, as occurred throughout hominin evolution. This paper reviews evidence linking exposomes to musculoskeletal health in subsistence populations, focusing on effects of physical activity, pathogens, diet, and reproduction. Chronic musculoskeletal conditions are common for humans and possibly prehistoric hominins but rarer in quadrupedal apes. We propose that transition to bipedalism ~6 to 8 million years ago constituted an early "mismatch scenario," increasing hominin susceptibility to musculoskeletal conditions vis-à-vis quadrupedal apes due to changes in mechanical loading environments. Mismatched musculoskeletal traits were not targets of selection because of trade-offs favoring bipedal extractive foraging and higher fertility.
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Affiliation(s)
- Jonathan Stieglitz
- Department of Social and Behavioral Sciences, Toulouse School of Economics, Institute for Advanced Study in Toulouse, Université Toulouse Capitole, Toulouse, France
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2
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Indo HP, Chatatikun M, Nakanishi I, Matsumoto KI, Imai M, Kawakami F, Kubo M, Abe H, Ichikawa H, Yonei Y, Beppu HJ, Minamiyama Y, Kanekura T, Ichikawa T, Phongphithakchai A, Udomwech L, Sukati S, Charong N, Somsak V, Tangpong J, Nomura S, Majima HJ. The Roles of Mitochondria in Human Being's Life and Aging. Biomolecules 2024; 14:1317. [PMID: 39456251 PMCID: PMC11506671 DOI: 10.3390/biom14101317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 10/03/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
The universe began 13.8 billion years ago, and Earth was born 4.6 billion years ago. Early traces of life were found as soon as 4.1 billion years ago; then, ~200,000 years ago, the human being was born. The evolution of life on earth was to become individual rather than cellular life. The birth of mitochondria made this possible to be the individual life. Since then, individuals have had a limited time of life. It was 1.4 billion years ago that a bacterial cell began living inside an archaeal host cell, a form of endosymbiosis that is the development of eukaryotic cells, which contain a nucleus and other membrane-bound compartments. The bacterium started to provide its host cell with additional energy, and the interaction eventually resulted in a eukaryotic cell, with both archaeal (the host cell) and bacterial (mitochondrial) origins still having genomes. The cells survived high concentrations of oxygen producing more energy inside the cell. Further, the roles of mitochondria in human being's life and aging will be discussed.
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Affiliation(s)
- Hiroko P. Indo
- Department of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City 890-8544, Japan; (H.P.I.)
- Amanogawa Galactic Astronomy Research Center (AGARC), Kagoshima University Graduate School of Sciences and Engineering, 1-21-40 Korimoto, Kagoshima 890-0065, Japan
| | - Moragot Chatatikun
- School of Allied Health Sciences, Walailak University, Thasala 80161, Thailand; (M.C.); (S.S.); (N.C.); (V.S.); (J.T.)
- Research Excellence Center for Innovation and Health Products (RECIHP), School of Allied Health Sciences, Walailak University, Thasala Nakhon Si Thammarat 80160, Thailand
| | - Ikuo Nakanishi
- Quantum RedOx Chemistry Team, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan;
| | - Ken-ichiro Matsumoto
- Quantitative RedOx Sensing Group, Department of Radiation Regulatory Science Research, Institute for Radiological Science (NIRS), National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
| | - Motoki Imai
- Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Japan
- Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0374, Japan
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Japan
| | - Fumitaka Kawakami
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Japan
- Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Japan
- Department of Health Administration, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Japan
| | - Makoto Kubo
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Japan
- Department of Environmental Microbiology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Japan
| | - Hiroshi Abe
- Department of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City 890-8544, Japan; (H.P.I.)
| | - Hiroshi Ichikawa
- Department of Medical Life Systems, Graduate School of Life and Medical Sciences, Doshishia University, Kyoto 610-0394, Japan
| | - Yoshikazu Yonei
- Anti-Aging Medical Research Center and Glycation Stress Research Center, Graduate School of Life and Medical Sciences, Doshisha University, Kyoto 610-0394, Japan
| | - Hisashi J. Beppu
- Dr. Beppu’s Oral Health Care & Anti-Aging Clinic, Chuo-ku, Tokyo 103-0027, Japan
| | - Yukiko Minamiyama
- Food Hygiene and Environmental Health Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Sakyo-ku, Kyoto 606-8522, Japan
| | - Takuro Kanekura
- Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
| | - Takafumi Ichikawa
- Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Japan
- Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Japan
| | - Atthaphong Phongphithakchai
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Lunla Udomwech
- School of Medicine, Walailak University, Thasala 80161, Thailand
| | - Suriyan Sukati
- School of Allied Health Sciences, Walailak University, Thasala 80161, Thailand; (M.C.); (S.S.); (N.C.); (V.S.); (J.T.)
- Hematology and Transfusion Science Research Center (HTSRC), School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Nurdina Charong
- School of Allied Health Sciences, Walailak University, Thasala 80161, Thailand; (M.C.); (S.S.); (N.C.); (V.S.); (J.T.)
- Hematology and Transfusion Science Research Center (HTSRC), School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Voravuth Somsak
- School of Allied Health Sciences, Walailak University, Thasala 80161, Thailand; (M.C.); (S.S.); (N.C.); (V.S.); (J.T.)
- Research Excellence Center for Innovation and Health Products (RECIHP), School of Allied Health Sciences, Walailak University, Thasala Nakhon Si Thammarat 80160, Thailand
| | - Jitbanjong Tangpong
- School of Allied Health Sciences, Walailak University, Thasala 80161, Thailand; (M.C.); (S.S.); (N.C.); (V.S.); (J.T.)
- Research Excellence Center for Innovation and Health Products (RECIHP), School of Allied Health Sciences, Walailak University, Thasala Nakhon Si Thammarat 80160, Thailand
| | - Sachiyo Nomura
- Department of Clinical Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan;
- Isotope Science Center, The University of Tokyo, 2-22-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
- Department of Gastrointestinal Surgery, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Hideyuki J. Majima
- School of Allied Health Sciences, Walailak University, Thasala 80161, Thailand; (M.C.); (S.S.); (N.C.); (V.S.); (J.T.)
- Research Excellence Center for Innovation and Health Products (RECIHP), School of Allied Health Sciences, Walailak University, Thasala Nakhon Si Thammarat 80160, Thailand
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Kriete A. Dissipative scaling of development and aging in multicellular organisms. Biosystems 2024; 237:105157. [PMID: 38367762 DOI: 10.1016/j.biosystems.2024.105157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 01/31/2024] [Accepted: 02/14/2024] [Indexed: 02/19/2024]
Abstract
Evolution, self-replication and ontogenesis are highly dynamic, irreversible and self-organizing processes dissipating energy. While progress has been made to decipher the role of thermodynamics in cellular fission, it is not yet clear how entropic balances shape organism growth and aging. This paper derives a general dissipation theory for the life history of organisms. It implies a self-regulated energy dissipation facilitating exponential growth within a hierarchical and entropy lowering self-organization. The theory predicts ceilings in energy expenditures imposed by geometric constrains, which promote thermal optimality during development, and a dissipative scaling across organisms consistent with ecological scaling laws combining isometric and allometric terms. The theory also illustrates how growing organisms can tolerate damage through continuous extension and production of new dissipative structures low in entropy. However, when organisms reduce their rate of cell division and reach a steady adult state, they become thermodynamically unstable, increase internal entropy by accumulating damage, and age.
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Affiliation(s)
- Andres Kriete
- School of Biomedical Engineering, Science and Health Systems, Drexel University, Bossone Research Center, 3141 Chestnut St., Philadelphia, PA, 19104, USA.
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Nakane D, Akiyama Y, Suzuki S, Miyazaki R, Akitsu T. Improvement of the SOD activity of the Cu 2+ complexes by hybridization with lysozyme and its hydrogen bond effect on the activity enhancement. Front Chem 2024; 11:1330833. [PMID: 38304569 PMCID: PMC10830756 DOI: 10.3389/fchem.2023.1330833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 12/27/2023] [Indexed: 02/03/2024] Open
Abstract
We prepared L-amino acids (L-valine and L-serine, respectively) based on the Schiff base Cu2+ complexes CuSV and CuSS in the absence/presence of hydroxyl groups and their imidazole-bound compounds CuSV-Imi and CuSS-Imi to reveal the effects of hydroxyl groups on SOD activity. The structural and spectroscopic features of the Cu2+ complexes were evaluated using X-ray crystallography, UV-vis spectroscopy, and EPR spectroscopy. The spectroscopic behavior upon addition of lysozyme indicated that both CuSV and CuSS were coordinated by the imidazole group of His15 in lysozyme at their equatorial position, leading to the formation of hybrid proteins with lysozyme. CuSS-Imi showed a higher SOD activity than CuSV-Imi, indicating that the hydroxyl group of CuSS-Imi played an important role in the disproportionation of O2 - ion. Hybridization of the Cu2+ complexes CuSV and CuSS with lysozyme resulted in higher SOD activity than that of CuSV-Imi and CuSS-Imi. The improvements in SOD activity suggest that there are cooperative effects between Cu2+ complexes and lysozyme.
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Affiliation(s)
- Daisuke Nakane
- Department of Chemistry, Faculty of Science, Tokyo University of Science, Tokyo, Japan
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Jové M, Mota-Martorell N, Fernàndez-Bernal A, Portero-Otin M, Barja G, Pamplona R. Phenotypic molecular features of long-lived animal species. Free Radic Biol Med 2023; 208:728-747. [PMID: 37748717 DOI: 10.1016/j.freeradbiomed.2023.09.023] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 09/12/2023] [Accepted: 09/21/2023] [Indexed: 09/27/2023]
Abstract
One of the challenges facing science/biology today is uncovering the molecular bases that support and determine animal and human longevity. Nature, in offering a diversity of animal species that differ in longevity by more than 5 orders of magnitude, is the best 'experimental laboratory' to achieve this aim. Mammals, in particular, can differ by more than 200-fold in longevity. For this reason, most of the available evidence on this topic derives from comparative physiology studies. But why can human beings, for instance, reach 120 years whereas rats only last at best 4 years? How does nature change the longevity of species? Longevity is a species-specific feature resulting from an evolutionary process. Long-lived animal species, including humans, show adaptations at all levels of biological organization, from metabolites to genome, supported by signaling and regulatory networks. The structural and functional features that define a long-lived species may suggest that longevity is a programmed biological property.
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Affiliation(s)
- Mariona Jové
- Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), University of Lleida (UdL), E25198, Lleida, Spain
| | - Natàlia Mota-Martorell
- Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), University of Lleida (UdL), E25198, Lleida, Spain
| | - Anna Fernàndez-Bernal
- Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), University of Lleida (UdL), E25198, Lleida, Spain
| | - Manuel Portero-Otin
- Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), University of Lleida (UdL), E25198, Lleida, Spain
| | - Gustavo Barja
- Department of Genetics, Physiology and Microbiology, Faculty of Biological Sciences, Complutense University of Madrid (UCM), E28040, Madrid, Spain
| | - Reinald Pamplona
- Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), University of Lleida (UdL), E25198, Lleida, Spain.
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Furuya T, Nakane D, Kitanishi K, Katsuumi N, Tsaturyan A, Shcherbakov IN, Unno M, Akitsu T. A novel hybrid protein composed of superoxide-dismutase-active Cu(II) complex and lysozyme. Sci Rep 2023; 13:6892. [PMID: 37106030 PMCID: PMC10140267 DOI: 10.1038/s41598-023-33926-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 04/20/2023] [Indexed: 04/29/2023] Open
Abstract
A novel hybrid protein composed of a superoxide dismutase-active Cu(II) complex (CuST) and lysozyme (CuST@lysozyme) was prepared. The results of the spectroscopic and electrochemical analyses confirmed that CuST binds to lysozyme. We determined the crystal structure of CuST@lysozyme at 0.92 Å resolution, which revealed that the His15 imidazole group of lysozyme binds to the Cu(II) center of CuST in the equatorial position. In addition, CuST was fixed in position by the weak axial coordination of the Thr89 hydroxyl group and the hydrogen bond between the guanidinium group of the Arg14 residue and the hydroxyl group of CuST. Furthermore, the combination of CuST with lysozyme did not decrease the superoxide dismutase activity of CuST. Based on the spectral, electrochemical, structural studies, and quantum chemical calculations, an O2- disproportionation mechanism catalyzed by CuST@lysozyme is proposed.
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Affiliation(s)
- Tetsundo Furuya
- Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan
| | - Daisuke Nakane
- Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan.
| | - Kenichi Kitanishi
- Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan
| | - Natsuki Katsuumi
- Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan
| | - Arshak Tsaturyan
- Université Jean Monnet Saint-Etienne, CNRS, Institut d Optique Graduate School, Laboratoire Hubert Curien UMR 5516, 42023, Saint-Étienne, France
- Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka Ave., Rostov-On-Don, 344090, Russia
| | - Igor N Shcherbakov
- Department of Chemistry, Southern Federal University, 7 Zorge Str., Rostov-On-Don, 344090, Russia
| | - Masaki Unno
- Graduate School of Science and Engineering, Ibaraki University, 4-12-1 Nakanarusawa, Hitachi, Ibaraki, 316-8511, Japan
| | - Takashiro Akitsu
- Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan.
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Serra V, Castrica M, Agradi S, Curone G, Vigo D, Di Giancamillo A, Modina SC, Riva F, Balzaretti CM, De Bellis R, Brecchia G, Pastorelli G. Antioxidant Activity of Different Tissues from Rabbits Fed Dietary Bovine Colostrum Supplementation. Animals (Basel) 2023; 13:ani13050850. [PMID: 36899707 PMCID: PMC10000081 DOI: 10.3390/ani13050850] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/23/2023] [Accepted: 02/24/2023] [Indexed: 03/03/2023] Open
Abstract
Recent advances in animal nutrition have indicated that bovine colostrum (BC), due to its content of macronutrients, micronutrients and bioactive compounds, is an excellent health supplement. To the best of our knowledge, no studies on the effect of BC on antioxidant status have been performed in rabbits. This study aimed to investigate the effect of two BC concentrations on antioxidant status and gene expression of antioxidant enzymes in some tissues of rabbits. Thirty New Zealand White male rabbits were randomly divided into three experimental diets, containing 0% (CON), 2.5%, and 5% of BC (BC-2.5 and BC-5, respectively). The activity of antioxidant enzymes in plasma (catalase: CAT; glutathione peroxidase: GPx; superoxide dismutase: SOD), and the enzymes' gene expression in the liver and longissimus dorsi muscle, were determined. Results showed no significant differences, neither in plasma nor in tissues. A significant tissue-related effect has been observed regarding the mRNA levels of SOD and GPx, which were higher in the LD (p = 0.022) and liver (p = 0.001), respectively. Further studies, considering modifications of the length and dosage of dietary BC supplementation, are required to update the current state of knowledge in rabbits, as well as to fully understand the potential value of BC for possible application in farming use.
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Affiliation(s)
- Valentina Serra
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università 6, 26900 Lodi, Italy
| | - Marta Castrica
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università 6, 26900 Lodi, Italy
| | - Stella Agradi
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università 6, 26900 Lodi, Italy
| | - Giulio Curone
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università 6, 26900 Lodi, Italy
| | - Daniele Vigo
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università 6, 26900 Lodi, Italy
| | - Alessia Di Giancamillo
- Department of Biomedical Sciences for Health, University of Milan, Via Mangiagalli 31, 20133 Milan, Italy
| | - Silvia Clotilde Modina
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università 6, 26900 Lodi, Italy
| | - Federica Riva
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università 6, 26900 Lodi, Italy
| | - Claudia Maria Balzaretti
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università 6, 26900 Lodi, Italy
| | - Roberta De Bellis
- Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Via A. Saffi 2, 61029 Urbino, Italy
| | - Gabriele Brecchia
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università 6, 26900 Lodi, Italy
- Correspondence: ; Tel.: +39-0250-334-583
| | - Grazia Pastorelli
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università 6, 26900 Lodi, Italy
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Tanshinone IIA Accomplished Protection against Radiation-Induced Cardiomyocyte Injury by Regulating the p38/p53 Pathway. Mediators Inflamm 2022; 2022:1478181. [PMID: 36046762 PMCID: PMC9424041 DOI: 10.1155/2022/1478181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 07/20/2022] [Accepted: 08/01/2022] [Indexed: 11/23/2022] Open
Abstract
Background Radiotherapy is one of the major strategies for treating tumors, and it inevitably causes damage to relevant tissues and organs during treatment. Radiation-induced heart disease (RIHD) refers to radiation-induced cardiovascular adverse effects caused by thoracic radiotherapy. Currently, there is no uniform standard in the treatment of RIHD. Methods In our group study, by administering a dose of 4 Gy radiation, we established a radiation injured cardiomyocyte model and explored the regulatory relationship between tanshinone IIA and p38 MAPK in cardiomyocyte injury. We assessed cell damage and proliferation using clonogenic assay and lactate dehydrogenase (LDH) release assay. The measures of antioxidant activity and oxidative stress were conducted using superoxide dismutase (SOD) and reactive oxygen species (ROS). The apoptosis rate and the relative expression of apoptotic proteins were conducted using flow cytometry and western blot. To assess p38 and p53 expressions and phosphorylation levels, western blot was performed. Results Experimental results suggested that tanshinone IIA restored cell proliferation in radiation-induced cardiomyocyte injury (∗∗P < 0.01), and the level of LDH release decreased (∗P < 0.05). Meanwhile, tanshinone IIA could decrease the ROS generation induced by radiation (∗∗P < 0.01) and upregulate the SOD level (∗∗P < 0.01). Again, tanshinone IIA reduced radiation-induced cardiomyocyte apoptosis (∗∗P < 0.01). Finally, tanshinone IIA downregulated radiation-induced p38/p53 overexpression (∗∗∗P < 0.001). Conclusions The treatment effects of tanshinone IIA against radiation-induced myocardial injury may be through the regulation of the p38/p53 pathway.
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9
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Boël M, Veyrunes F, Durieux AC, Freyssenet D, Voituron Y, Roussel D. Does high mitochondrial efficiency carry an oxidative cost? The case of the African pygmy mouse (Mus mattheyi). Comp Biochem Physiol A Mol Integr Physiol 2021; 264:111111. [PMID: 34748935 DOI: 10.1016/j.cbpa.2021.111111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/01/2021] [Accepted: 11/01/2021] [Indexed: 10/19/2022]
Abstract
Skeletal muscle mitochondria of the African pygmy mouse Mus mattheyi exhibit markedly reduced oxygen consumption and ATP synthesis rates but a higher mitochondrial efficiency than what would be expected from allometric trends. In the present study, we assessed whether such reduction of mitochondrial activity in M. mattheyi can limit the oxidative stress associated with an increased generation of mitochondrial reactive oxygen species. We conducted a comparative study of mitochondrial oxygen consumption, H2O2 release, and electron leak (%H2O2/O) in skeletal muscle mitochondria isolated from the extremely small African pygmy mouse (M. mattheyi, ~5 g) and Mus musculus, which is a larger Mus species (~25 g). Mitochondria were energized with pyruvate, malate, and succinate, after which fluxes were measured at different steady-state rates of oxidative phosphorylation. Overall, M. mattheyi exhibited lower oxidative activity and higher electron leak than M. musculus, while the H2O2 release did not differ significantly between these two Mus species. We further found that the high coupling efficiency of skeletal muscle mitochondria from M. mattheyi was associated with high electron leak. Nevertheless, data also show that, despite the higher electron leak, the lower mitochondrial respiratory capacity of M. mattheyi limits the cost of a net increase in H2O2 release, which is lower than that expected for a mammals of this size.
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Affiliation(s)
- Mélanie Boël
- Univ Lyon, Université Claude Bernard Lyon 1, CNRS, ENTPE, UMR 5023 LEHNA, F-69622 Villeurbanne, France.
| | - Frédéric Veyrunes
- Université Montpellier, IRD, EPHE, CNRS, UMR 5554 Institut des Sciences de l'Evolution de Montpellier, F-34095 Montpellier, France
| | - Anne-Cécile Durieux
- Inter-University Laboratory of Human Movement Biology, Univ Lyon, Université Jean Monnet Saint-Etienne, F-42023 Saint-Etienne, France
| | - Damien Freyssenet
- Inter-University Laboratory of Human Movement Biology, Univ Lyon, Université Jean Monnet Saint-Etienne, F-42023 Saint-Etienne, France
| | - Yann Voituron
- Univ Lyon, Université Claude Bernard Lyon 1, CNRS, ENTPE, UMR 5023 LEHNA, F-69622 Villeurbanne, France
| | - Damien Roussel
- Univ Lyon, Université Claude Bernard Lyon 1, CNRS, ENTPE, UMR 5023 LEHNA, F-69622 Villeurbanne, France.
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10
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Squitti R, Faller P, Hureau C, Granzotto A, White AR, Kepp KP. Copper Imbalance in Alzheimer's Disease and Its Link with the Amyloid Hypothesis: Towards a Combined Clinical, Chemical, and Genetic Etiology. J Alzheimers Dis 2021; 83:23-41. [PMID: 34219710 DOI: 10.3233/jad-201556] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The cause of Alzheimer's disease (AD) is incompletely defined. To date, no mono-causal treatment has so far reached its primary clinical endpoints, probably due to the complexity and diverse neuropathology contributing to the neurodegenerative process. In the present paper, we describe the plausible etiological role of copper (Cu) imbalance in the disease. Cu imbalance is strongly associated with neurodegeneration in dementia, but a complete biochemical etiology consistent with the clinical, chemical, and genetic data is required to support a causative association, rather than just correlation with disease. We hypothesize that a Cu imbalance in the aging human brain evolves as a gradual shift from bound metal ion pools, associated with both loss of energy production and antioxidant function, to pools of loosely bound metal ions, involved in gain-of-function oxidative stress, a shift that may be aggravated by chemical aging. We explain how this may cause mitochondrial deficits, energy depletion of high-energy demanding neurons, and aggravated protein misfolding/oligomerization to produce different clinical consequences shaped by the severity of risk factors, additional comorbidities, and combinations with other types of pathology. Cu imbalance should be viewed and integrated with concomitant genetic risk factors, aging, metabolic abnormalities, energetic deficits, neuroinflammation, and the relation to tau, prion proteins, α-synuclein, TAR DNA binding protein-43 (TDP-43) as well as systemic comorbidity. Specifically, the Amyloid Hypothesis is strongly intertwined with Cu imbalance because amyloid-β protein precursor (AβPP)/Aβ are probable Cu/Zn binding proteins with a potential role as natural Cu/Zn buffering proteins (loss of function), and via the plausible pathogenic role of Cu-Aβ.
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Affiliation(s)
- Rosanna Squitti
- Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Peter Faller
- Institut de Chimie, UMR 7177, CNRS, Université de Strasbourg, Strasbourg, France
| | | | - Alberto Granzotto
- Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.,Center for Advanced Sciences and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy.,Department of Neuroscience, Imaging, and Clinical Sciences (DNISC), Laboratory of Molecular Neurology, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy
| | - Anthony R White
- Mental Health Program, QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia
| | - Kasper P Kepp
- DTU Chemistry, Technical University of Denmark, Lyngby, Denmark
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11
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Kraft TS, Stieglitz J, Trumble BC, Garcia AR, Kaplan H, Gurven M. Multi-system physiological dysregulation and ageing in a subsistence population. Philos Trans R Soc Lond B Biol Sci 2020; 375:20190610. [PMID: 32951553 PMCID: PMC7540955 DOI: 10.1098/rstb.2019.0610] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/15/2020] [Indexed: 12/12/2022] Open
Abstract
Humans have the longest post-reproductive lifespans and lowest rates of actuarial ageing among primates. Understanding the links between slow actuarial ageing and physiological change is critical for improving the human 'healthspan'. Physiological dysregulation may be a key feature of ageing in industrialized populations with high burdens of chronic 'diseases of civilization', but little is known about age trajectories of physiological condition in subsistence populations with limited access to public health infrastructure. To better characterize human physiological dysregulation, we examined age trajectories of 40 biomarkers spanning the immune (n = 13 biomarkers), cardiometabolic (n = 14), musculoskeletal (n = 6) and other (n = 7) systems among Tsimane forager-horticulturalists of the Bolivian Amazon using mixed cross-sectional and longitudinal data (n = 22 115 observations). We characterized age-related changes using a multi-system statistical index of physiological dysregulation (Mahalanobis distance; Dm) that increases with age in both humans and other primates. Although individual biomarkers showed varied age profiles, we found a robust increase in age-related dysregulation for Tsimane (β = 0.17-0.18) that was marginally faster than that reported for an industrialized Western sample (β = 0.14-0.16), but slower than that of other non-human primates. We found minimal sex differences in the pace or average level of dysregulation for Tsimane. Our findings highlight some conserved patterns of physiological dysregulation in humans, consistent with the notion that somatic ageing exhibits species-typical patterns, despite cross-cultural variation in environmental exposures, lifestyles and mortality. This article is part of the theme issue 'Evolution of the primate ageing process'.
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Affiliation(s)
- Thomas S. Kraft
- Integrative Anthropological Sciences Unit, Department of Anthropology, University of California-Santa Barbara, Santa Barbara, CA 93106, USA
| | | | - Benjamin C. Trumble
- Center for Evolution and Medicine, School of Human Evolution and Social Change, Arizona State University, Tempe, AZ 85287, USA
| | - Angela R. Garcia
- Integrative Anthropological Sciences Unit, Department of Anthropology, University of California-Santa Barbara, Santa Barbara, CA 93106, USA
- Center for Evolution and Medicine, School of Human Evolution and Social Change, Arizona State University, Tempe, AZ 85287, USA
| | - Hillard Kaplan
- Economic Science Institute, Chapman University, One University Drive, Orange, CA 92866, USA
| | - Michael Gurven
- Integrative Anthropological Sciences Unit, Department of Anthropology, University of California-Santa Barbara, Santa Barbara, CA 93106, USA
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12
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Yanase S, Yasuda K, Ishii N. Interaction between the ins/IGF-1 and p38 MAPK signaling pathways in molecular compensation of sod genes and modulation related to intracellular ROS levels in C. elegans. Biochem Biophys Rep 2020; 23:100796. [PMID: 32875124 PMCID: PMC7451853 DOI: 10.1016/j.bbrep.2020.100796] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 06/04/2020] [Accepted: 08/02/2020] [Indexed: 01/28/2023] Open
Abstract
Superoxide dismutases, which catalytically remove intracellular superoxide radicals by the disproportionation of molecular oxygen and hydrogen peroxide, are encoded by the sod-1 to -5 genes in the nematode C. elegans. Expression of the sod genes is mutually compensatory for the modulation of intracellular oxidative stress during aging. Interestingly, several-fold higher expression of the sod-1 to -4 was induced in a sod-5 deletion mutant, despite the low expression levels of sod-5 in wild-type animals. Consequently, this molecular compensation facilitated recovery of lifespan in the sod-5 mutant. In previous reports, two transcription factors DAF-16 and SKN-1 are associated with the compensatory expression of sod genes, which are downstream targets of the ins/IGF-1 and p38 MAPK signaling pathways activated under oxidative and heavy metal stresses, respectively. Here, we show that p38 MAPK signaling regulates induction of not only the direct expression of sod-1, -2 and -4 but also the indirect modulation of DAF-16 targets, such as sod-3 and -5 genes. Moreover, a SKN-1 target, the insulin peptide gene ins-5, partially mediates the expression of DAF-16 targets via p38 MAPK signaling. These findings suggest that the interaction of ins/IGF-1 and p38 MAPK signaling pathways plays an important role in the fine-tuning of molecular compensation among sod genes to protect against mitochondrial oxidative damage during aging.
Mitochondrial ROS is removed by SODs during aging. Expression of sod genes in C. elegans related to lifespan maintenance. Interaction of the ins/IGF-1 and p38 MAPK signalings regulates the fine-tuning of sod genes expression. ins-5 of SKN-1 target encodes an agonist of ins/IGF-1 signaling.
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Affiliation(s)
- Sumino Yanase
- Department of Health Science, Daito Bunka University School of Sports & Health Science, 560 Iwadono, Higashi-matsuyama, Saitama, 355-8501, Japan
| | - Kayo Yasuda
- Department of Health Management, Tokai University Undergraduate School of Health Studies, 4-1-1 Kitakaname, Hiratsuka, Kanagawa, 259-1292, Japan
| | - Naoaki Ishii
- Department of Health Management, Tokai University Undergraduate School of Health Studies, 4-1-1 Kitakaname, Hiratsuka, Kanagawa, 259-1292, Japan
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13
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Voituron Y, Boël M, Roussel D. Mitochondrial threshold for H 2O 2 release in skeletal muscle of mammals. Mitochondrion 2020; 54:85-91. [PMID: 32738356 DOI: 10.1016/j.mito.2020.07.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 07/08/2020] [Accepted: 07/27/2020] [Indexed: 11/25/2022]
Abstract
The aim of the study was to evaluate the interplay between mitochondrial respiration and H2O2 release during the transition from basal non-phosphorylating to maximal phosphorylating states. We conducted a large scale comparative study of mitochondrial oxygen consumption, H2O2 release and electron leak (% H2O2/O) in skeletal muscle mitochondria isolated from mammal species ranging from 7 g to 500 kg. Mitochondrial fluxes were measured at different steady state rates in presence of pyruvate, malate, and succinate as respiratory substrates. Every species exhibited a burst of H2O2 release from skeletal muscle mitochondria at a low rate of oxidative phosphorylation, essentially once the activity of mitochondrial oxidative phosphorylation reached 26% of the maximal respiration. This threshold for ROS generation thus appears as a general characteristic of skeletal muscle mitochondria in mammals. These findings may have implications in situations promoting succinate accumulation within mitochondria, such as ischemia or hypoxia.
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Affiliation(s)
- Yann Voituron
- Université de Lyon, Université Claude Bernard Lyon 1, CNRS, ENTPE, UMR5023 LEHNA, F-69622 Villeurbanne, France.
| | - Mélanie Boël
- Université de Lyon, Université Claude Bernard Lyon 1, CNRS, ENTPE, UMR5023 LEHNA, F-69622 Villeurbanne, France
| | - Damien Roussel
- Université de Lyon, Université Claude Bernard Lyon 1, CNRS, ENTPE, UMR5023 LEHNA, F-69622 Villeurbanne, France
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14
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Yang JL, Li XL, Jiang FL, Gong T, Chen JJ, Chen TJ, Zhu P. High-level soluble expression of human Cu,Zn superoxide dismutase with high activity in Escherichia coli. World J Microbiol Biotechnol 2020; 36:106. [DOI: 10.1007/s11274-020-02883-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 06/29/2020] [Indexed: 12/12/2022]
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15
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Abstract
Darwin's theory of evolution emphasized that positive selection of functional proficiency provides the fitness that ultimately determines the structure of life, a view that has dominated biochemical thinking of enzymes as perfectly optimized for their specific functions. The 20th-century modern synthesis, structural biology, and the central dogma explained the machinery of evolution, and nearly neutral theory explained how selection competes with random fixation dynamics that produce molecular clocks essential e.g. for dating evolutionary histories. However, quantitative proteomics revealed that selection pressures not relating to optimal function play much larger roles than previously thought, acting perhaps most importantly via protein expression levels. This paper first summarizes recent progress in the 21st century toward recovering this universal selection pressure. Then, the paper argues that proteome cost minimization is the dominant, underlying 'non-function' selection pressure controlling most of the evolution of already functionally adapted living systems. A theory of proteome cost minimization is described and argued to have consequences for understanding evolutionary trade-offs, aging, cancer, and neurodegenerative protein-misfolding diseases.
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16
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Kunath S, Moosmann B. What is the rate-limiting step towards aging? Chemical reaction kinetics might reconcile contradictory observations in experimental aging research. GeroScience 2019; 42:857-866. [PMID: 30809734 DOI: 10.1007/s11357-019-00058-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Accepted: 02/11/2019] [Indexed: 02/05/2023] Open
Abstract
Modern geroscience is divided as regards the validity of the free radical theory of aging. Thermodynamic arguments and observations from comparative zoology support it, whereas results from experimental manipulations in representative animal species sometimes strongly contradict it. From a comparison of the multi-step aging process with a linear metabolic pathway (glycolysis), we here argue that the identification of the rate-limiting kinetic steps of the aging cascade is essential to understand the overall flux through the cascade, i.e., the rate of aging. Examining free radical reactions as a case in point, these reactions usually occur as chain reactions with three kinetically independent steps: initiation, propagation, and termination, each of which can be rate-limiting. Revisiting the major arguments in favor and against a role of free radicals in aging, we find that the majority of arguments in favor point to radical propagation as relevant and rate-limiting, whereas almost all arguments in disfavor are based on experimental manipulations of radical initiation or radical termination which turned out to be ineffective. We conclude that the overall lack of efficacy of antioxidant supplementation (which fosters termination) and antioxidant enzyme overexpression (which inhibits initiation) in longevity studies is attributable to the fact that initiation and termination are not the rate-limiting steps of the aging cascade. The biological and evolutionary plausibility of this interpretation is discussed. In summary, radical propagation is predicted to be rate-limiting for aging and should be explored in more detail.
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Affiliation(s)
- Sascha Kunath
- Evolutionary Biochemistry and Redox Medicine, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany
| | - Bernd Moosmann
- Evolutionary Biochemistry and Redox Medicine, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany.
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17
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Zhou YZ, Xue LY, Gao L, Qin XM, Du GH. Ginger extract extends the lifespan of Drosophila melanogaster through antioxidation and ameliorating metabolic dysfunction. J Funct Foods 2018. [DOI: 10.1016/j.jff.2018.08.040] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
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18
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Dasmeh P, Kepp KP. Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes. Cell Mol Life Sci 2017; 74:3023-3037. [PMID: 28389720 PMCID: PMC11107616 DOI: 10.1007/s00018-017-2519-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 03/17/2017] [Accepted: 04/03/2017] [Indexed: 12/14/2022]
Abstract
Positive (adaptive) selection has recently been implied in human superoxide dismutase 1 (SOD1), a highly abundant antioxidant protein with energy signaling and antiaging functions, one of very few examples of direct selection on a human protein product (exon); the molecular drivers of this selection are unknown. We mapped 30 extant SOD1 sequences to the recently established mammalian species tree and inferred ancestors, key substitutions, and signatures of selection during the protein's evolution. We detected elevated substitution rates leading to great apes (Hominidae) at ~1 per 2 million years, significantly higher than in other primates and rodents, although these paradoxically generally evolve much faster. The high evolutionary rate was partly due to relaxation of some selection pressures and partly to distinct positive selection of SOD1 in great apes. We then show that higher stability and net charge and changes at the dimer interface were selectively introduced upon separation from old world monkeys and lesser apes (gibbons). Consequently, human, chimpanzee and gorilla SOD1s have a net charge of -6 at physiological pH, whereas the closely related gibbons and macaques have -3. These features consistently point towards selection against the malicious aggregation effects of elevated SOD1 levels in long-living great apes. The findings mirror the impact of human SOD1 mutations that reduce net charge and/or stability and cause ALS, a motor neuron disease characterized by oxidative stress and SOD1 aggregates and triggered by aging. Our study thus marks an example of direct selection for a particular chemical phenotype (high net charge and stability) in a single human protein with possible implications for the evolution of aging.
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Affiliation(s)
- Pouria Dasmeh
- Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA
- Department of Biochemistry and Cedergren Center for Bioinformatics and Genomics, Faculty of Medicine, University of Montreal, 2900 Edouard-Montpetit, Montreal, QC, H3T 1J4, Canada
| | - Kasper P Kepp
- Technical University of Denmark, DTU Chemistry, 2800, Kongens Lyngby, Denmark.
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19
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Enany S, Yoshida Y, Tateishi Y, Ozeki Y, Nishiyama A, Savitskaya A, Yamaguchi T, Ohara Y, Yamamoto T, Ato M, Matsumoto S. Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions. Sci Rep 2017; 7:6810. [PMID: 28754952 PMCID: PMC5533761 DOI: 10.1038/s41598-017-06480-w] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Accepted: 06/13/2017] [Indexed: 11/09/2022] Open
Abstract
Bacteria can proliferate perpetually without ageing, but they also face conditions where they must persist. Mycobacteria can survive for a long period. This state appears during mycobacterial diseases such as tuberculosis and leprosy, which are chronic and develop after long-term persistent infections. However, the fundamental mechanisms of the long-term living of mycobacteria are unknown. Every Mycobacterium species expresses Mycobacterial DNA-binding protein 1 (MDP1), a histone-like nucleoid associated protein. Mycobacterium smegmatis is a saprophytic fast grower and used as a model of mycobacterial persistence, since it shares the characteristics of the long-term survival observed in pathogenic mycobacteria. Here we show that MDP1-deficient M. smegmatis dies more rapidly than the parental strain after entering stationary phase. Proteomic analyses revealed 21 upregulated proteins with more than 3-fold in MDP1-deficient strain, including DnaA, a replication initiator, NDH, a NADH dehydrogenase that catalyzes downhill electron transfer, Fas1, a critical fatty acid synthase, and antioxidants such as AhpC and KatG. Biochemical analyses showed elevated levels of DNA and ATP syntheses, a decreased NADH/NAD+ ratio, and a loss of resistance to oxidative stress in the MDP1-knockout strain. This study suggests the importance of MDP1-dependent simultaneous control of the cellular functions in the long-term survival of mycobacteria.
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Affiliation(s)
- Shymaa Enany
- Department of Bacteriology, Niigata University School of Medicine, 1-757, Asahimachi-Dori, Chuo-ku, Niigata, Niigata, 951-9510, Japan.,Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, 41522, Ismailia, Egypt
| | - Yutaka Yoshida
- Department of Structural Pathology, Kidney Research Center, 1-757, Asahimachi-Dori, Chuo-ku, Niigata, Niigata, 951-9510, Japan
| | - Yoshitaka Tateishi
- Department of Bacteriology, Niigata University School of Medicine, 1-757, Asahimachi-Dori, Chuo-ku, Niigata, Niigata, 951-9510, Japan
| | - Yuriko Ozeki
- Department of Bacteriology, Niigata University School of Medicine, 1-757, Asahimachi-Dori, Chuo-ku, Niigata, Niigata, 951-9510, Japan
| | - Akihito Nishiyama
- Department of Bacteriology, Niigata University School of Medicine, 1-757, Asahimachi-Dori, Chuo-ku, Niigata, Niigata, 951-9510, Japan.
| | - Anna Savitskaya
- Department of Bacteriology, Niigata University School of Medicine, 1-757, Asahimachi-Dori, Chuo-ku, Niigata, Niigata, 951-9510, Japan
| | - Takehiro Yamaguchi
- Department of Bacteriology, Niigata University School of Medicine, 1-757, Asahimachi-Dori, Chuo-ku, Niigata, Niigata, 951-9510, Japan
| | - Yukiko Ohara
- Department of Bacteriology, Niigata University School of Medicine, 1-757, Asahimachi-Dori, Chuo-ku, Niigata, Niigata, 951-9510, Japan
| | - Tadashi Yamamoto
- Biofluid Biomarker Center, Institute of Social innovation and Co-operation, Niigata University, 8050 Ikarashi 2-no-cho, Nishi-ku, Niigata, Niigata, 950-2181, Japan
| | - Manabu Ato
- Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan
| | - Sohkichi Matsumoto
- Department of Bacteriology, Niigata University School of Medicine, 1-757, Asahimachi-Dori, Chuo-ku, Niigata, Niigata, 951-9510, Japan.
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20
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Nguyen HVT, Chen Q, Paletta JT, Harvey P, Jiang Y, Zhang H, Boska MD, Ottaviani MF, Jasanoff A, Rajca A, Johnson JA. Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors. ACS CENTRAL SCIENCE 2017; 3:800-811. [PMID: 28776023 PMCID: PMC5532724 DOI: 10.1021/acscentsci.7b00253] [Citation(s) in RCA: 123] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Indexed: 05/18/2023]
Abstract
Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxide-functionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor in vivo stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous tumors up to 20 h following systemic administration such that MRI contrast on par with metal-based agents is observed. BASP-ORCAs are, to our knowledge, the first nitroxide MRI contrast agents capable of tumor imaging over long time periods using clinical high-field 1H MRI techniques.
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Affiliation(s)
- Hung V.-T. Nguyen
- Department
of Chemistry, Department of Biological Engineering, Department of Brain
and Cognitive Sciences, and Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
| | - Qixian Chen
- Department
of Chemistry, Department of Biological Engineering, Department of Brain
and Cognitive Sciences, and Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
| | - Joseph T. Paletta
- Department
of Chemistry, University of Nebraska, Lincoln, Nebraska 68588, United States
| | - Peter Harvey
- Department
of Chemistry, Department of Biological Engineering, Department of Brain
and Cognitive Sciences, and Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
| | - Yivan Jiang
- Department
of Chemistry, Department of Biological Engineering, Department of Brain
and Cognitive Sciences, and Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
| | - Hui Zhang
- Department
of Chemistry, University of Nebraska, Lincoln, Nebraska 68588, United States
| | - Michael D. Boska
- Department
of Radiology, University of Nebraska Medical
Center, Omaha, Nebraska 68198, United
States
| | | | - Alan Jasanoff
- Department
of Chemistry, Department of Biological Engineering, Department of Brain
and Cognitive Sciences, and Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
| | - Andrzej Rajca
- Department
of Chemistry, University of Nebraska, Lincoln, Nebraska 68588, United States
| | - Jeremiah A. Johnson
- Department
of Chemistry, Department of Biological Engineering, Department of Brain
and Cognitive Sciences, and Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
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21
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Yamauchi Y, Matsuno T, Omata K, Satoh T. Relationship between hyposalivation and oxidative stress in aging mice. J Clin Biochem Nutr 2017; 61:40-46. [PMID: 28751808 PMCID: PMC5525015 DOI: 10.3164/jcbn.16-79] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 09/28/2016] [Indexed: 12/21/2022] Open
Abstract
The increase in oxidative stress that accompanies aging has been implicated in the abnormal advance of aging and in the onset of various systemic diseases. However, the details of what effects the increase in oxidative stress that accompanies aging has on saliva secretion are not known. In this study, naturally aging mice were used to examine the stimulated whole saliva flow rate, saliva and serum oxidative stress, antioxidant level, submandibular gland H-E staining, and immunofluorescence staining to investigate the effect of aging on the volume of saliva secretion and the relationship with oxidative stress, as well as the effect of aging on the structure of salivary gland tissue. The stimulated whole saliva flow rate decreased significantly with age. Also, oxidative stress increased significantly with age. Antioxidant levels, however, decreased significantly with age. Structural changes of the submandibular gland accompanying aging included atrophy of parenchyma cells and fatty degeneration and fibrosis of stroma, and the submandibular gland weight ratio decreased. These results suggest that oxidative stress increases with age, not just systemically but also locally in the submandibular gland, and that oxidative stress causes changes in the structure of the salivary gland and is involved in hyposalivation.
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Affiliation(s)
- Yoshitaka Yamauchi
- Department of Oral and Maxillofacial Surgery, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan
| | - Tomonori Matsuno
- Department of Oral and Maxillofacial Surgery, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan
| | - Kazuhiko Omata
- Department of Oral and Maxillofacial Surgery, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan
| | - Tazuko Satoh
- Department of Oral and Maxillofacial Surgery, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan
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22
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Sasaki T, Awaji T, Shimada K, Sasaki H. Increase of reactive oxygen species generation in cerebral cortex slices after the transiently enhanced metabolic activity. Neurosci Res 2017; 123:55-64. [PMID: 28499835 DOI: 10.1016/j.neures.2017.04.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Revised: 03/31/2017] [Accepted: 04/28/2017] [Indexed: 10/19/2022]
Abstract
Under certain conditions such as hypoxia-reoxygenation, the generation of reactive oxygen species (ROS) increases following hypoxia caused by a decreased oxygen supply. As another hypoxic condition, an excess neural activity status including epileptic seizure induces a decrease in tissue oxygen partial pressure (pO2) caused by enhanced oxygen utilization; however, whether ROS generation increases following the hypoxic status induced by transiently enhanced energy metabolism in brain tissue currently remains unknown. We herein investigated ROS-dependent chemiluminescence in cerebral cortex slices during the restoration of transiently enhanced energy metabolism induced by a high-potassium treatment with tissue pO2 changes and redox balance. ROS generation in the tissue was enhanced after high-potassium-induced hypoxia, but not by the reversed order of the treatment: control-potassium then high-potassium treatment, high-potassium treatment alone, and control-potassium treatment alone. The high-potassium treatment induced a transient decrease in tissue pO2 and a shift in the tissue redox balance towards reduction. The transient shift in the tissue redox balance towards reduction with enhanced metabolic activity and its recovery may correlate with ROS generation. This phenomenon may mimic ROS generation following the hypoxic status induced by transiently enhanced energy metabolism.
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Affiliation(s)
- Toru Sasaki
- Department of Medical Engineering and Technology, Kitasato University School of Allied of Health Sciences, 1-15-1 Kitasato, Sagamihara, Kanagawa 252-0373, Japan; Research Team for Mechanism of Aging, Redox Research, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi, Tokyo 173-0015, Japan.
| | - Takuji Awaji
- Department of Medical Engineering and Technology, Kitasato University School of Allied of Health Sciences, 1-15-1 Kitasato, Sagamihara, Kanagawa 252-0373, Japan
| | - Kazuyoshi Shimada
- Department of Medical Engineering and Technology, Kitasato University School of Allied of Health Sciences, 1-15-1 Kitasato, Sagamihara, Kanagawa 252-0373, Japan
| | - Haruyo Sasaki
- Department of Medical Engineering and Technology, Kitasato University School of Allied of Health Sciences, 1-15-1 Kitasato, Sagamihara, Kanagawa 252-0373, Japan
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23
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Wu YS, Liau SY, Huang CT, Nan FH. Beta 1,3/1,6-glucan and vitamin C immunostimulate the non-specific immune response of white shrimp (Litopenaeus vannamei). FISH & SHELLFISH IMMUNOLOGY 2016; 57:269-277. [PMID: 27561624 DOI: 10.1016/j.fsi.2016.08.046] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 08/16/2016] [Accepted: 08/20/2016] [Indexed: 06/06/2023]
Abstract
This study mainly evaluated the effects of orally administered beta 1,3/1,6-glucan and vitamin C on the nonspecific immune responses of white shrimp (Litopenaeus vannamei). In this study, we found that the white shrimp oral administration with 1 g/kg of beta 1,3/1,6-glucan effectively enhanced O2(-) production and phenoloxidase and superoxide dismutase activity. Shrimp were oral administration with 0.2 g/kg of vitamin C presented beneficial nonspecific immune responses and enzyme activity and also observed in the beta 1,3/1,6-glucan treatment groups. Consequently, we compared the alterations in the immune activity between the beta 1,3/1,6-glucan and vitamin C groups and the evidence illustrated that combination of beta 1,3/1,6-glucan and vitamin C presented an additive effect on inducing the nonspecific immune responses of white shrimp.
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Affiliation(s)
- Yu-Sheng Wu
- Department of Aquaculture, National Taiwan Ocean University, Keelung 20248, Taiwan
| | - Shu-Yu Liau
- Department of Aquaculture, National Taiwan Ocean University, Keelung 20248, Taiwan
| | - Cheng-Ting Huang
- Department of Aquaculture, National Taiwan Ocean University, Keelung 20248, Taiwan
| | - Fan-Hua Nan
- Department of Aquaculture, National Taiwan Ocean University, Keelung 20248, Taiwan.
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24
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Abstract
The inflammatory state after burn injury is characterized by an increase in capillary permeability that results in protein and fluid leakage into the interstitial space, increasing resuscitative requirements. Although the mechanisms underlying increased capillary permeability are complex, damage from reactive oxygen species plays a major role and has been successfully attenuated with antioxidant therapy in several disease processes. However, the utility of antioxidants in burn treatment remains unclear. Vitamin C is a promising antioxidant candidate that has been examined in burn resuscitation studies and shows efficacy in reducing the fluid requirements in the acute phase after burn injury.
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Affiliation(s)
- Julie A Rizzo
- United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX 78234, USA; Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
| | - Matthew P Rowan
- United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX 78234, USA
| | - Ian R Driscoll
- United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX 78234, USA; Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
| | - Kevin K Chung
- United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX 78234, USA; Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
| | - Bruce C Friedman
- JM Still Burn Center at Doctor's Hospital, 3651 Wheeler Road, Augusta, GA 30909, USA
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25
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Chandra M, Gupta V, Rath AK, Vaish AK, Srimal RC, Pandev VC, Ghatak A, Sircar AR, Bhardwaj RS, Singhal SS. Effect of Oral Vitamin E on Oxy-Free Radical Status in Acute Myocardial Infarction. Asian Cardiovasc Thorac Ann 2016. [DOI: 10.1177/021849239500300406] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The present work was conducted to study the status of oxidative stress (oxy-free radicals) in 24 patients with acute myocardial infarction and 12 matched healthy control patients and furthermore evaluate the effect of oral vitamin E on altered oxyfree radicals in these patients. The parameters assessed for oxy-free radical status were superoxide anion and malonyldialdehyde. These were found to be increased during acute myocardial infarction and this increment had a normalizing trend with the passage of time. It was found that the administration of vitamin E accelerated the normalizing trend of both superoxide anion and malonyldialdehyde. Thus, vitamin E has an antioxidant effect in acute myocardial infarction.
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Affiliation(s)
- Mahesh Chandra
- Department of Medicine, K G Medical College, Lucknow, India
| | - Vivek Gupta
- Institute of Cardiology, GSVM Medical College, Kanpur, India
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26
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Lubrano V, Balzan S. Enzymatic antioxidant system in vascular inflammation and coronary artery disease. World J Exp Med 2015; 5:218-224. [PMID: 26618108 PMCID: PMC4655251 DOI: 10.5493/wjem.v5.i4.218] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 08/07/2015] [Accepted: 11/04/2015] [Indexed: 02/06/2023] Open
Abstract
In biological systems there is a balance between the production and neutralization of reactive oxygen species (ROS). This balance is maintained by the presence of natural antioxidants and antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase. The enhancement of lipid peroxidation or the decrease of antioxidant protection present in metabolic diseases or bad lifestyle can induce endothelial dysfunction and atherosclerosis. Clinical studies have shown that oxidative stress can increase ROS reducing the formation of antioxidant defences, especially in subjects with coronary artery disease (CAD). Some observation indicated that in the early stages of the disease there is a homeostatic up-regulation of the antioxidant enzyme system in response to increased free radicals to prevent vascular damage. As soon as free radicals get to chronically elevated levels, this compensation ceases. Therefore, SOD and the other enzymes may represent a good therapeutic target against ROS, but they are not useful markers for the diagnosis of CAD. In conclusion antioxidant enzymes are reduced in presence of metabolic disease and CAD. However the existence of genes that promote their enzymatic activity could contribute to create new drugs for the treatment of damage caused by metabolic diseases or lifestyle that increases the plasma ROS levels.
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27
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Metabolic Field (Schrodinger); an explanatory platform for biology: Based on lecture at Trinity College, Dublin, Ireland, July 18, 2012. Med Hypotheses 2015; 85:894-7. [PMID: 26404869 DOI: 10.1016/j.mehy.2015.09.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 08/14/2015] [Accepted: 09/12/2015] [Indexed: 02/08/2023]
Abstract
Metabolism represents the nexus of fundamental physical forces, which while present in all structure and function require new explanatory emergent principles, which, so far, cannot be predicted or derived solely from description of chemistry and physics. Metabolism is essentially concerned with the transduction of energy flows with respect to time, space, and matter. Language models and metaphors contribute to construction of scientific explanation within biology. The concept of a metabolic field yields a deeper, broader, more quantitative integrated theoretical framework leading to novel predictive models of systems biology.
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28
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Barja G. The mitochondrial free radical theory of aging. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2015; 127:1-27. [PMID: 25149212 DOI: 10.1016/b978-0-12-394625-6.00001-5] [Citation(s) in RCA: 132] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The mitochondrial free radical theory of aging is reviewed. Only two parameters currently correlate with species longevity in the right sense: the mitochondrial rate of reactive oxygen species (mitROS) production and the degree of fatty acid unsaturation of tissue membranes. Both are low in long-lived animals. In addition, the best-known manipulation that extends longevity, dietary restriction, also decreases the rate of mitROS production and oxidative damage to mtDNA. The same occurs during protein restriction as well as during methionine restriction. These two manipulations also increase maximum longevity in rodents. The decrease in mitROS generation and oxidative stress that takes place in caloric restriction seems to be due to restriction of a single dietary substance: methionine. The information available supports a mitochondrial free radical theory of aging focused on low generation of endogenous damage and low sensitivity of membranes to oxidation in long-lived animals.
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Affiliation(s)
- Gustavo Barja
- Department of Animal Physiology II, Faculty of Biological Sciences, Complutense University, Madrid Spain
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29
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Indo HP, Yen HC, Nakanishi I, Matsumoto KI, Tamura M, Nagano Y, Matsui H, Gusev O, Cornette R, Okuda T, Minamiyama Y, Ichikawa H, Suenaga S, Oki M, Sato T, Ozawa T, Clair DKS, Majima HJ. A mitochondrial superoxide theory for oxidative stress diseases and aging. J Clin Biochem Nutr 2014; 56:1-7. [PMID: 25834301 PMCID: PMC4306659 DOI: 10.3164/jcbn.14-42] [Citation(s) in RCA: 230] [Impact Index Per Article: 20.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 08/08/2014] [Indexed: 11/26/2022] Open
Abstract
Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O2•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.
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Affiliation(s)
- Hiroko P Indo
- Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan ; Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan ; Graduate Center of Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40506, USA
| | - Hsiu-Chuan Yen
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan
| | - Ikuo Nakanishi
- Radio-Redox-Response Research Team, Advanced Particle Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan
| | - Ken-Ichiro Matsumoto
- Radio-Redox-Response Research Team, Advanced Particle Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan
| | - Masato Tamura
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Yumiko Nagano
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Hirofumi Matsui
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Oleg Gusev
- Department of Invertebrates Zoology and Functional Morphology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremevskaya str., 17 Kazan 420-008, Russia ; Japan Aerospace Exploration Agency, Institute of Space and Astronautical Science, ISS Science Project Office, Ibaraki 305-8505, Japan ; Anhydrobiosis Research Unit, National Institute of Agrobiological Sciences, Ohwashi 1-2, Tsukuba, Ibaraki 305-8634, Japan
| | - Richard Cornette
- Anhydrobiosis Research Unit, National Institute of Agrobiological Sciences, Ohwashi 1-2, Tsukuba, Ibaraki 305-8634, Japan
| | - Takashi Okuda
- Anhydrobiosis Research Unit, National Institute of Agrobiological Sciences, Ohwashi 1-2, Tsukuba, Ibaraki 305-8634, Japan
| | - Yukiko Minamiyama
- Food Hygiene and Environmental Health Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Sakyo-ku, Kyoto 606-8522, Japan
| | - Hiroshi Ichikawa
- Department of Medical Life Systems, Graduate School of Life and Medical Sciences, Doshishia University, Kyoto 610-0394, Japan
| | - Shigeaki Suenaga
- Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan
| | - Misato Oki
- Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan
| | - Tsuyoshi Sato
- Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan
| | - Toshihiko Ozawa
- Division of Oxidative Stress Research, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
| | - Daret K St Clair
- Graduate Center of Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40506, USA
| | - Hideyuki J Majima
- Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan ; Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan
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30
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Musacco-Sebio R, Ferrarotti N, Saporito-Magriñá C, Semprine J, Fuda J, Torti H, Boveris A, Repetto MG. Oxidative damage to rat brain in iron and copper overloads. Metallomics 2014; 6:1410-6. [DOI: 10.1039/c3mt00378g] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Increased cytosolic levels of Fe2+, Cu+and H2O2are central to the hypothesis that Fe and Cu toxicities are mediated by OH˙ formation and oxidative damage due to phospholipids and proteins oxidation.
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Affiliation(s)
- Rosario Musacco-Sebio
- Department of General and Inorganic Chemistry
- University of Buenos Aires
- Buenos Aires, Argentina
| | - Nidia Ferrarotti
- Department of General and Inorganic Chemistry
- University of Buenos Aires
- Buenos Aires, Argentina
- Laboratory of Clinical Immunology
- Department of Clinical Biochemistry
| | | | - Jimena Semprine
- Department of General and Inorganic Chemistry
- University of Buenos Aires
- Buenos Aires, Argentina
| | - Julián Fuda
- Department of Physics
- School of Pharmacy and Biochemistry
- University of Buenos Aires
- Buenos Aires, Argentina
| | - Horacio Torti
- Department of Physics
- School of Pharmacy and Biochemistry
- University of Buenos Aires
- Buenos Aires, Argentina
| | - Alberto Boveris
- Institute of Biochemistry and Molecular Medicine (IBIMOL, UBA-CONICET)
- University of Buenos Aires
- Buenos Aires, Argentina
| | - Marisa G. Repetto
- Department of General and Inorganic Chemistry
- University of Buenos Aires
- Buenos Aires, Argentina
- Institute of Biochemistry and Molecular Medicine (IBIMOL, UBA-CONICET)
- University of Buenos Aires
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31
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Lewis KN, Andziak B, Yang T, Buffenstein R. The naked mole-rat response to oxidative stress: just deal with it. Antioxid Redox Signal 2013; 19:1388-99. [PMID: 23025341 PMCID: PMC3791056 DOI: 10.1089/ars.2012.4911] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
SIGNIFICANCE The oxidative stress theory of aging has been the most widely accepted theory of aging providing insights into why we age and die for over 50 years, despite mounting evidence from a multitude of species indicating that there is no direct relationship between reactive oxygen species (ROS) and longevity. Here we explore how different species, including the longest lived rodent, the naked mole-rat, have defied the most predominant aging theory. RECENT ADVANCES In the case of extremely long-lived naked mole-rat, levels of ROS production are found to be similar to mice, antioxidant defenses unexceptional, and even under constitutive conditions, naked mole-rats combine a pro-oxidant intracellular milieu with high, steady state levels of oxidative damage. Clearly, naked mole-rats can tolerate this level of oxidative stress and must have mechanisms in place to prevent its translation into potentially lethal diseases. CRITICAL ISSUES In addition to the naked mole-rat, other species from across the phylogenetic spectrum and even certain mouse strains do not support this theory. Moreover, overexpressing or knocking down antioxidant levels alters levels of oxidative damage and even cancer incidence, but does not modulate lifespan. FUTURE DIRECTIONS Perhaps, it is not oxidative stress that modulates healthspan and longevity, but other cytoprotective mechanisms that allow animals to deal with high levels of oxidative damage and stress, and nevertheless live long, relatively healthy lifespans. Studying these mechanisms in uniquely long-lived species, like the naked mole-rat, may help us tease out the key contributors to aging and longevity.
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Affiliation(s)
- Kaitlyn N Lewis
- 1 Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio , San Antonio, Texas
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32
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Barja G. Updating the mitochondrial free radical theory of aging: an integrated view, key aspects, and confounding concepts. Antioxid Redox Signal 2013; 19:1420-45. [PMID: 23642158 PMCID: PMC3791058 DOI: 10.1089/ars.2012.5148] [Citation(s) in RCA: 224] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Revised: 04/11/2013] [Accepted: 05/05/2013] [Indexed: 01/12/2023]
Abstract
An updated version of the mitochondrial free radical theory of aging (MFRTA) and longevity is reviewed. Key aspects of the theory are emphasized. Another main focus concerns common misconceptions that can mislead investigators from other specialties, even to wrongly discard the theory. Those different issues include (i) the main reactive oxygen species (ROS)-generating site in the respiratory chain in relation to aging and longevity: complex I; (ii) the close vicinity or even contact between that site and the mitochondrial DNA, in relation to the lack of local efficacy of antioxidants and to sub-cellular compartmentation; (iii) the relationship between mitochondrial ROS production and oxygen consumption; (iv) recent criticisms on the MFRTA; (v) the widespread assumption that ROS are simple "by-products" of the mitochondrial respiratory chain; (vi) the unnecessary postulation of "vicious cycle" hypotheses of mitochondrial ROS generation which are not central to the free radical theory of aging; and (vii) the role of DNA repair concerning endogenous versus exogenous damage. After considering the large body of data already available, two general characteristics responsible for the high maintenance degree of long-lived animals emerge: (i) a low generation rate of endogenous damage: and (ii) the possession of tissue macromolecules that are highly resistant to oxidative modification.
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Affiliation(s)
- Gustavo Barja
- Department of Animal Physiology II, Faculty of Biological Sciences, Complutense University , Madrid, Spain
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33
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Stuart JA, Liang P, Luo X, Page MM, Gallagher EJ, Christoff CA, Robb EL. A comparative cellular and molecular biology of longevity database. AGE (DORDRECHT, NETHERLANDS) 2013; 35:1937-1947. [PMID: 22836712 PMCID: PMC3776122 DOI: 10.1007/s11357-012-9458-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2011] [Accepted: 07/09/2012] [Indexed: 06/01/2023]
Abstract
Discovering key cellular and molecular traits that promote longevity is a major goal of aging and longevity research. One experimental strategy is to determine which traits have been selected during the evolution of longevity in naturally long-lived animal species. This comparative approach has been applied to lifespan research for nearly four decades, yielding hundreds of datasets describing aspects of cell and molecular biology hypothesized to relate to animal longevity. Here, we introduce a Comparative Cellular and Molecular Biology of Longevity Database, available at ( http://genomics.brocku.ca/ccmbl/ ), as a compendium of comparative cell and molecular data presented in the context of longevity. This open access database will facilitate the meta-analysis of amalgamated datasets using standardized maximum lifespan (MLSP) data (from AnAge). The first edition contains over 800 data records describing experimental measurements of cellular stress resistance, reactive oxygen species metabolism, membrane composition, protein homeostasis, and genome homeostasis as they relate to vertebrate species MLSP. The purpose of this review is to introduce the database and briefly demonstrate its use in the meta-analysis of combined datasets.
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Affiliation(s)
- Jeffrey A Stuart
- Department of Biological Sciences, Brock University, St. Catharines, ON, Canada, L2S 3A1,
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34
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Schneeberger K, Czirják GÁ, Voigt CC. Inflammatory challenge increases measures of oxidative stress in a free-ranging, long-lived mammal. ACTA ACUST UNITED AC 2013; 216:4514-9. [PMID: 24031067 DOI: 10.1242/jeb.090837] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Oxidative stress - the imbalance between reactive oxygen species (ROS) and neutralising antioxidants - has been under debate as the main cause of ageing in aerobial organisms. The level of ROS should increase during infection as part of the activation of an immune response, leading to oxidative damage to proteins, lipids and DNA. Yet, it is unknown how long-lived organisms, especially mammals, cope with oxidative stress. Bats are known to carry a variety of zoonotic pathogens and at the same time are, despite their high mass-specific basal metabolic rate, unusually long lived, which may be partly the result of low oxidative damage of organs. Here, we asked whether an immune challenge causes oxidative stress in free-ranging bats, measuring two oxidative stress markers. We injected 20 short-tailed fruit bats (Carollia perspicillata) with bacterially derived lipopolysaccharide (LPS) and 20 individuals with phosphate-buffered saline solution (PBS) as a control. Individuals injected with LPS showed an immune reaction by increased white blood cell count after 24 h, whereas there was no significant change in leukocyte count in control animals. The biological antioxidant potential (BAP) remained the same in both groups, but reactive oxygen metabolites (ROMs) increased after treatment with LPS, indicating a significant increase in oxidative stress in animals when mounting an immune reaction toward the inflammatory challenge. Control individuals did not show a change in oxidative stress markers. We conclude that in a long-lived mammal, even high concentrations of antioxidants do not immediately neutralise free radicals produced during a cellular immune response. Thus, fighting an infection may lead to oxidative stress in bats.
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Affiliation(s)
- Karin Schneeberger
- Leibniz Institute for Zoo and Wildlife Research, Alfred-Kowalke-Strasse 17, 10315 Berlin, Germany
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35
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Sanz A, Trenzado C, Botello Castro H, López-Rodríguez M, Tierno de Figueroa J. Relationship between brain and liver oxidative state and maximum lifespan potential of different fish species. Comp Biochem Physiol A Mol Integr Physiol 2013; 165:358-64. [DOI: 10.1016/j.cbpa.2013.04.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2012] [Revised: 04/12/2013] [Accepted: 04/18/2013] [Indexed: 10/26/2022]
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36
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A cytoprotective perspective on longevity regulation. Trends Cell Biol 2013; 23:409-20. [PMID: 23726168 DOI: 10.1016/j.tcb.2013.04.007] [Citation(s) in RCA: 106] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2013] [Revised: 04/17/2013] [Accepted: 04/18/2013] [Indexed: 02/07/2023]
Abstract
There are many mechanisms of lifespan extension, including the disruption of insulin/insulin-like growth factor 1 (IGF-1) signaling, metabolism, translation, and feeding. Despite the disparate functions of these pathways, inhibition of each induces responses that buffer stress and damage. Here, emphasizing data from genetic analyses in Caenorhabditis elegans, we explore the effectors and upstream regulatory components of numerous cytoprotective mechanisms activated as major elements of longevity programs, including detoxification, innate immunity, proteostasis, and oxidative stress response. We show that their induction underpins longevity extension across functionally diverse triggers and across species. Intertwined with the evolution of longevity, cytoprotective pathways are coupled to the surveillance of core cellular components, with important implications in normal and aberrant responses to drugs, chemicals, and pathogens.
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37
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Yokozawa T, Chen CP. Evidence suggesting a nitric oxide-scavenging activity for traditional crude drugs, and action mechanisms of Sanguisorbae Radix against oxidative stress and aging. J Am Aging Assoc 2013; 24:19-30. [PMID: 23604872 DOI: 10.1007/s11357-001-0003-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
In this series of experiments, we found that Sanguisorbae Radix extract possesses strong free radical-scavenging activity in vitro and in vivo. This crude drug protected against renal disease, which is closely associated with excessive generation of reactive oxygen species. We also showed that Sanguisorbae Radix extract can suppress lipid peroxidation and stimulate an antioxidant defense ability in SAM, suggesting that this crude drug may be an effective agent for ameliorating the pathological conditions related to excessive generation of free radicals and oxidant damage, particularly in the aging process.
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Affiliation(s)
- T Yokozawa
- Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930-0194 Japan
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38
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Muller F. The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging. J Am Aging Assoc 2013; 23:227-53. [PMID: 23604868 DOI: 10.1007/s11357-000-0022-9] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Most biogerontologists agree that oxygen (and nitrogen) free radicals play a major role in the process of aging. The evidence strongly suggests that the electron transport chain, located in the inner mitochondrial membrane, is the major source of reactive oxygen species in animal cells. It has been reported that there exists an inverse correlation between the rate of superoxide/hydrogen peroxide production by mitochondria and the maximum longevity of mammalian species. However, no correlation or most frequently an inverse correlation exists between the amount of antioxidant enzymes and maximum longevity. Although overexpression of the antioxidant enzymes SOD1 and CAT (as well as SOD1 alone) have been successful at extending maximum lifespan in Drosophila, this has not been the case in mice. Several labs have overexpressed SOD1 and failed to see a positive effect on longevity. An explanation for this failure is that there is some level of superoxide damage that is not preventable by SOD, such as that initiated by the hydroperoxyl radical inside the lipid bilayer, and that accumulation of this damage is responsible for aging. I therefore suggest an alternative approach to testing the free radical theory of aging in mammals. Instead of trying to increase the amount of antioxidant enzymes, I suggest using molecular biology/transgenics to decrease the rate of superoxide production, which in the context of the free radical theory of aging would be expected to increase longevity. This paper aims to summarize what is known about the nature and mechanisms of superoxide production and what genes are involved in controlling the rate of superoxide production.
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Affiliation(s)
- F Muller
- Laboratory of David M. Kramer, Institute of Biological Chemistry, Washington State University, Pullman, WA 99164 USA
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39
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Radak Z, Zhao Z, Koltai E, Ohno H, Atalay M. Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling. Antioxid Redox Signal 2013; 18:1208-46. [PMID: 22978553 PMCID: PMC3579386 DOI: 10.1089/ars.2011.4498] [Citation(s) in RCA: 411] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The complexity of human DNA has been affected by aerobic metabolism, including endurance exercise and oxygen toxicity. Aerobic endurance exercise could play an important role in the evolution of Homo sapiens, and oxygen was not important just for survival, but it was crucial to redox-mediated adaptation. The metabolic challenge during physical exercise results in an elevated generation of reactive oxygen species (ROS) that are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair, which at moderate levels generate physiological responses. Several factors of mitochondrial biogenesis, such as peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), mitogen-activated protein kinase, and SIRT1, are modulated by exercise-associated changes in the redox milieu. PGC-1α activation could result in decreased oxidative challenge, either by upregulation of antioxidant enzymes and/or by an increased number of mitochondria that allows lower levels of respiratory activity for the same degree of ATP generation. Endogenous thiol antioxidants glutathione and thioredoxin are modulated with high oxygen consumption and ROS generation during physical exercise, controlling cellular function through redox-sensitive signaling and protein-protein interactions. Endurance exercise-related angiogenesis, up to a significant degree, is regulated by ROS-mediated activation of hypoxia-inducible factor 1α. Moreover, the exercise-associated ROS production could be important to DNA methylation and post-translation modifications of histone residues, which create heritable adaptive conditions based on epigenetic features of chromosomes. Accumulating data indicate that exercise with moderate intensity has systemic and complex health-promoting effects, which undoubtedly involve regulation of redox homeostasis and signaling.
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Affiliation(s)
- Zsolt Radak
- Faculty of Physical Education and Sport Science, Institute of Sport Science, Semmelweis University, Budapest, Hungary.
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Csiszar A, Podlutsky A, Podlutskaya N, Sonntag WE, Merlin SZ, Philipp EER, Doyle K, Davila A, Recchia FA, Ballabh P, Pinto JT, Ungvari Z. Testing the oxidative stress hypothesis of aging in primate fibroblasts: is there a correlation between species longevity and cellular ROS production? J Gerontol A Biol Sci Med Sci 2012; 67:841-52. [PMID: 22219516 PMCID: PMC3403864 DOI: 10.1093/gerona/glr216] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2011] [Accepted: 11/02/2011] [Indexed: 01/31/2023] Open
Abstract
The present study was conducted to test predictions of the oxidative stress theory of aging assessing reactive oxygen species production and oxidative stress resistance in cultured fibroblasts from 13 primate species ranging in body size from 0.25 to 120 kg and in longevity from 20 to 90 years. We assessed both basal and stress-induced reactive oxygen species production in fibroblasts from five great apes (human, chimpanzee, bonobo, gorilla, and orangutan), four Old World monkeys (baboon, rhesus and crested black macaques, and patas monkey), three New World monkeys (common marmoset, red-bellied tamarin, and woolly monkey), and one lemur (ring-tailed lemur). Measurements of cellular MitoSox fluorescence, an indicator of mitochondrial superoxide (O2(·-)) generation, showed an inverse correlation between longevity and steady state or metabolic stress-induced mitochondrial O2(·-) production, but this correlation was lost when the effects of body mass were removed, and the data were analyzed using phylogenetically independent contrasts. Fibroblasts from longer-lived primate species also exhibited superior resistance to H(2)O(2)-induced apoptotic cell death than cells from shorter-living primates. After correction for body mass and lack of phylogenetic independence, this correlation, although still discernible, fell short of significance by regression analysis. Thus, increased longevity in this sample of primates is not causally associated with low cellular reactive oxygen species generation, but further studies are warranted to test the association between increased cellular resistance to oxidative stressor and primate longevity.
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Affiliation(s)
- Anna Csiszar
- Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Science Center, 975 NE 10th Street, BRC-1315A, Oklahoma City, OK 73104, USA.
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41
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Primate enamel evinces long period biological timing and regulation of life history. J Theor Biol 2012; 305:131-44. [DOI: 10.1016/j.jtbi.2012.04.007] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2012] [Revised: 03/28/2012] [Accepted: 04/05/2012] [Indexed: 11/21/2022]
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Yun JH, Hwang ES, Kim GH. Effects of Chrysanthemum indicum L. Extract on the Function of Osteoblastic MC3T3-E1 Cells under Oxidative Stress Induced by Hydrogen PeroxideJee. ACTA ACUST UNITED AC 2012. [DOI: 10.9721/kjfst.2012.44.1.082] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Montgomery MK, Buttemer WA, Hulbert AJ. Does the oxidative stress theory of aging explain longevity differences in birds? II. Antioxidant systems and oxidative damage. Exp Gerontol 2012; 47:211-22. [PMID: 22230489 DOI: 10.1016/j.exger.2011.11.014] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2011] [Revised: 11/17/2011] [Accepted: 11/23/2011] [Indexed: 12/11/2022]
Abstract
The oxidative damage hypothesis of aging posits that the accumulation of oxidative damage is a determinant of an animal species' maximum lifespan potential (MLSP). Recent findings in extremely long-living mammal species such as naked mole-rats challenge this proposition. Among birds, parrots are exceptionally long-living with an average MLSP of 25 years, and with some species living more than 70 years. By contrast, quail are among the shortest living bird species, averaging about 5-fold lower MLSP than parrots. To test if parrots have correspondingly (i) superior antioxidant protection and (ii) lower levels of oxidative damage compared to similar-sized quail, we measured (i) total antioxidant capacity, uric acid and reduced glutathione (GSH) levels, as well as the activities of enzymatic antioxidants (superoxide dismutase, glutathione peroxidase and catalase), and (ii) markers of mitochondrial DNA damage (8-OHdG), protein damage (protein carbonyls) and lipid peroxidation (lipid hydroperoxides and TBARS) in three species of long-living parrots and compared these results to corresponding measures in two species of short-living quails (average MLSP=5.5 years). All birds were fed the same diet to exclude differences in dietary antioxidant levels. Tissue antioxidants and oxidative damage were determined both 'per mg protein' and 'per g tissue'. Only glutathione peroxidase was consistently higher in tissues of the long-living parrots and suggests higher protection against the harmful effects of hydroperoxides, which might be important for parrot longevity. The levels of oxidative damage were mostly statistically indistinguishable between parrots and quails (67%), occasionally higher (25%), but rarely lower (8%) in the parrots. Despite indications of higher protection against some aspects of oxidative stress in the parrots, the pronounced longevity of parrots appears to be independent of their antioxidant mechanisms and their accumulation of oxidative damage.
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Affiliation(s)
- Magdalene K Montgomery
- School of Biological Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia.
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44
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Matsumoto S. [Analysis of molecular mechanisms of the virulence and growth coordination of Mycobacterium tuberculosis]. Nihon Saikingaku Zasshi 2011; 66:531-537. [PMID: 22214749 DOI: 10.3412/jsb.66.531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Affiliation(s)
- Sohkichi Matsumoto
- Department of Bacteriology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
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Ranjini MS, Hosamani R, Muralidhara, Ramachandra NB. Differential susceptibility of a few members of thenasuta–albomicanscomplex ofDrosophilato paraquat-induced lethality and oxidative stress. Genome 2011; 54:829-35. [PMID: 21961920 DOI: 10.1139/g11-049] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
The evolution of karyotypically stabilized short-lived (SL) and long-lived (LL) cytoraces in the laboratory have been established and validated through our previous lifespan studies. In the present investigation, we examined the possible reason(s) for the differential longevity among selected members of SL and LL cytoraces, employing the well known paraquat (PQ) resistance bioassay. Exposure of these races to varying concentrations of PQ revealed relatively higher resistance among LL cytoraces than SL cytoraces, as evident by the lower incidence of mortality. Biochemical analysis for endogenous markers of oxidative stress revealed that LL-2 cytorace exhibited lower reactive oxygen species (ROS) and lipid peroxidation (LPO) levels, higher activity levels of superoxide dismutase (SOD), and coupled with higher levels of reduced glutathione (GSH) compared with the levels found in SL-2 cytorace. These findings suggest that the higher susceptibility of SL cytoraces to PQ challenge may be, at least in part, related to the higher endogenous levels of oxidative stress markers. Although the precise mechanisms responsible for the longer longevity among LL cytoraces of the nasuta–albomicans complex of Drosophila merits further investigation, our data suggest that the relatively longer lifespan may be related to the status of endogenous markers that renders them more resistant towards oxidative-stress-mediated lethality, as evident in the PQ assay.
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Affiliation(s)
- Mysore S. Ranjini
- Unit on Evolution and Genetics Laboratory, Department of Studies in Zoology, University of Mysore, Manasagangotri, Mysore 570 006, India
| | - Ravikumar Hosamani
- Department of Biochemistry and Nutrition, Central Food Technological Research Institute (CFTRI), Mysore 570020, India
| | - Muralidhara
- Department of Biochemistry and Nutrition, Central Food Technological Research Institute (CFTRI), Mysore 570020, India
| | - Nallur B. Ramachandra
- Unit on Evolution and Genetics Laboratory, Department of Studies in Zoology, University of Mysore, Manasagangotri, Mysore 570 006, India
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Pamplona R, Costantini D. Molecular and structural antioxidant defenses against oxidative stress in animals. Am J Physiol Regul Integr Comp Physiol 2011; 301:R843-63. [PMID: 21775650 DOI: 10.1152/ajpregu.00034.2011] [Citation(s) in RCA: 213] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
In this review, it is our aim 1) to describe the high diversity in molecular and structural antioxidant defenses against oxidative stress in animals, 2) to extend the traditional concept of antioxidant to other structural and functional factors affecting the "whole" organism, 3) to incorporate, when supportable by evidence, mechanisms into models of life-history trade-offs and maternal/epigenetic inheritance, 4) to highlight the importance of studying the biochemical integration of redox systems, and 5) to discuss the link between maximum life span and antioxidant defenses. The traditional concept of antioxidant defenses emphasizes the importance of the chemical nature of molecules with antioxidant properties. Research in the past 20 years shows that animals have also evolved a high diversity in structural defenses that should be incorporated in research on antioxidant responses to reactive species. Although there is a high diversity in antioxidant defenses, many of them are evolutionary conserved across animal taxa. In particular, enzymatic defenses and heat shock response mediated by proteins show a low degree of variation. Importantly, activation of an antioxidant response may be also energetically and nutrient demanding. So knowledge of antioxidant mechanisms could allow us to identify and to quantify any underlying costs, which can help explain life-history trade-offs. Moreover, the study of inheritance mechanisms of antioxidant mechanisms has clear potential to evaluate the contribution of epigenetic mechanisms to stress response phenotype variation.
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Affiliation(s)
- Reinald Pamplona
- Department of Experimental Medicine, University of Lleida Biomedical Research Institute of Lleida, Lleida, Spain
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Miller RA, Williams JB, Kiklevich JV, Austad S, Harper JM. Comparative cellular biogerontology: primer and prospectus. Ageing Res Rev 2011; 10:181-90. [PMID: 20109583 PMCID: PMC2889236 DOI: 10.1016/j.arr.2010.01.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2009] [Revised: 01/19/2010] [Accepted: 01/20/2010] [Indexed: 01/25/2023]
Abstract
Most prior work on the biological basis of aging has focused on describing differences between young and old individuals but provided only limited insight into the mechanisms controlling the rate of aging. Natural selection has produced a goldmine of experimental material, in the form of species of differing aging rate, whose longevity can vary by 10-fold or more within mammalian orders, but these resources remain largely unexplored at the cellular level. In this review article we focus on one approach to comparative biogerontology: the strategy of evaluating the properties of cultured cells from organisms of varying lifespan and aging rate. In addition, we discuss problems associated with the analysis and interpretations of interspecific variation of cellular trait data among species with disparate longevity. Given the impressive array of 'natural experiments' in aging rate, overcoming the technical and conceptual obstacles confronting research in comparative cellular gerontology will be well worth the effort.
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Affiliation(s)
- Richard A Miller
- Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, United States
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Davis RM, Matsumoto S, Bernardo M, Sowers A, Matsumoto KI, Krishna MC, Mitchell JB. Magnetic resonance imaging of organic contrast agents in mice: capturing the whole-body redox landscape. Free Radic Biol Med 2011; 50:459-68. [PMID: 21130158 PMCID: PMC3031128 DOI: 10.1016/j.freeradbiomed.2010.11.028] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2010] [Revised: 11/15/2010] [Accepted: 11/22/2010] [Indexed: 11/18/2022]
Abstract
Nitroxides are a class of stable free radicals that have several biomedical applications including radioprotection and noninvasive assessment of tissue redox status. For both of these applications, it is necessary to understand the in vivo biodistribution and reduction of nitroxides. In this study, magnetic resonance imaging was used to compare tissue accumulation (concentration) and reduction of two commonly studied nitroxides: the piperidine nitroxide Tempol and the pyrrolidine nitroxide 3-CP. It was found that 3-CP was reduced 3 to 11 times slower (depending on the tissue) than Tempol in vivo and that maximum tissue concentration varies substantially between tissues (0.6-7.2mM). For a given tissue, the maximum concentration usually did not vary between the two nitroxides. Furthermore, using electron paramagnetic resonance spectroscopy, we showed that the nitroxide reduction rate depends only weakly on cellular pO(2) in the oxygen range expected in vivo. These observations, taken with the marked variation in nitroxide reduction rates observed between tissues, suggest that tissue pO(2) is not a major determinant of the nitroxide reduction rate in vivo. For the purpose of redox imaging, 3-CP was shown to be an optimal choice based on the achievable concentrations and bioreduction observed in vivo.
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Affiliation(s)
- Ryan M Davis
- Radiation Biology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.
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Navarro A, Boveris A. Brain mitochondrial dysfunction in aging, neurodegeneration, and Parkinson's disease. Front Aging Neurosci 2010; 2. [PMID: 20890446 PMCID: PMC2947925 DOI: 10.3389/fnagi.2010.00034] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2010] [Accepted: 07/14/2010] [Indexed: 12/28/2022] Open
Abstract
Brain senescence and neurodegeneration occur with a mitochondrial dysfunction characterized by impaired electron transfer and by oxidative damage. Brain mitochondria of old animals show decreased rates of electron transfer in complexes I and IV, decreased membrane potential, increased content of the oxidation products of phospholipids and proteins and increased size and fragility. This impairment, with complex I inactivation and oxidative damage, is named “complex I syndrome” and is recognized as characteristic of mammalian brain aging and of neurodegenerative diseases. Mitochondrial dysfunction is more marked in brain areas as rat hippocampus and frontal cortex, in human cortex in Parkinson's disease and dementia with Lewy bodies, and in substantia nigra in Parkinson's disease. The molecular mechanisms involved in complex I inactivation include the synergistic inactivations produced by ONOO− mediated reactions, by reactions with free radical intermediates of lipid peroxidation and by amine–aldehyde adduction reactions. The accumulation of oxidation products prompts the idea of antioxidant therapies. High doses of vitamin E produce a significant protection of complex I activity and mitochondrial function in rats and mice, and with improvement of neurological functions and increased median life span in mice. Mitochondria-targeted antioxidants, as the Skulachev cations covalently attached to vitamin E, ubiquinone and PBN and the SS tetrapeptides, are negatively charged and accumulate in mitochondria where they exert their antioxidant effects. Activation of the cellular mechanisms that regulate mitochondrial biogenesis is another potential therapeutic strategy, since the process generates organelles devoid of oxidation products and with full enzymatic activity and capacity for ATP production.
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Affiliation(s)
- Ana Navarro
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Cádiz , Cádiz, Spain
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Ectoines in cell stress protection: uses and biotechnological production. Biotechnol Adv 2010; 28:782-801. [PMID: 20600783 DOI: 10.1016/j.biotechadv.2010.06.005] [Citation(s) in RCA: 253] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2010] [Revised: 06/18/2010] [Accepted: 06/22/2010] [Indexed: 11/20/2022]
Abstract
Microorganisms produce and accumulate compatible solutes aiming at protecting themselves from environmental stresses. Among them, the wide spread in nature ectoines are receiving increasing attention by the scientific community because of their multiple applications. In fact, increasing commercial demand has led to a multiplication of efforts in order to improve processes for their production. In this review, the importance of current and potential applications of ectoines as protecting agents for macromolecules, cells and tissues, together with their potential as therapeutic agents for certain diseases are analyzed and current theories for the understanding of the molecular basis of their biological activity are discussed. The genetic, biochemical and environmental determinants of ectoines biosynthesis by natural and engineered producers are described. The major limitations of current bioprocesses used for ectoines production are discussed, with emphasis on the different microorganisms, environments, molecular engineering and fermentation strategies used to optimize the production and recovery of ectoines. The combined application of both bioprocess and metabolic engineering strategies, allowing a deeper understanding of the main factors controlling the production process is also stated. Finally, this review aims to summarize and update the state of the art in ectoines uses and applications and industrial scale production using bacteria, emphasizing the importance of reactor design and operation strategies, together with the metabolic engineering aspects and the need for feedback between wet and in silico work to optimize bioproduction.
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