When a theory of aging ages badly
Jérôme Lapointe,Siegfried Hekimi +1 more
TLDR
It is reasonable to now consider the MFRTA as refuted and that it is time to use the insight gained by many years of testing this theory to develop new views as to the physiological causes of aging.Abstract:
According to the widely acknowledged mitochondrial free radical theory of aging (MFRTA), the macromolecular damage that results from the production of toxic reactive oxygen species (ROS) during cellular respiration is the cause of aging. However, although it is clear that oxidative damage increases during aging, the fundamental question regarding whether mitochondrial oxidative stress is in any way causal to the aging process remains unresolved. An increasing number of studies on long-lived vertebrate species, mutants and transgenic animals have seriously challenged the pervasive MFRTA. Here, we describe some of these new results, including those pertaining to the phenotype of the long-lived Mclk1
+/−
mice, which appear irreconcilable with the MFRTA. Thus, we believe that it is reasonable to now consider the MFRTA as refuted and that it is time to use the insight gained by many years of testing this theory to develop new views as to the physiological causes of aging.read more
Citations
More filters
Journal ArticleDOI
The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology
TL;DR: The importance of ROS and RNS to plant biology has been relatively little appreciated in the plasma biomedicine community, but it appears that there are opportunities for useful applications of plasmas in this area as well.
Journal ArticleDOI
Declining NAD + Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging
Ana P. Gomes,Ana P. Gomes,Nathan L. Price,Alvin J. Y. Ling,Javid Moslehi,Magdalene K. Montgomery,Luis A. Rajman,James P. White,João S. Teodoro,Christiane D. Wrann,Basil P. Hubbard,Evi M. Mercken,Carlos M. Palmeira,Rafael de Cabo,Anabela P. Rolo,Nigel Turner,Eric L. Bell,David A. Sinclair,David A. Sinclair +18 more
TL;DR: It is shown that, during aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits, and an alternate PGC-1α/β-independent pathway of nuclear-mitochondrial communication contributes to the decline in mitochondrial function with age.
Journal ArticleDOI
Reactive species in non-equilibrium atmospheric-pressure plasmas: Generation, transport, and biological effects
Xinpei Lu,Xinpei Lu,George V. Naidis,Mounir Laroussi,Stephan Reuter,David B. Graves,Ken Ostrikov +6 more
TL;DR: In this paper, the most important mechanisms of generation and transport of the key species in the plasmas of atmospheric-pressure plasma jets and other non-equilibrium atmospheric pressure plasms are introduced and examined from the viewpoint of their applications in plasma hygiene and medicine and other relevant fields.
Journal ArticleDOI
Oxidative Stress, Mitochondrial Dysfunction, and Aging
Hang Cui,Yahui Kong,Hong Zhang +2 more
TL;DR: The current understanding of the interplay between ROS and mitochondria is presented and their potential impact on aging and age-related diseases is discussed.
Journal ArticleDOI
Extending life span by increasing oxidative stress.
TL;DR: Results here suggest that antioxidant supplements that prevent these ROS signals interfere with the health-promoting and life-span-extending capabilities of calorie restriction and physical exercise, and question Harman's Free Radical Theory of Aging.
References
More filters
Journal ArticleDOI
The Free Radical Theory of Aging Matures
Kenneth B. Beckman,Bruce N. Ames +1 more
TL;DR: The status of the free radical theory of aging is reviewed, by categorizing the literature in terms of the various types of experiments that have been performed, which include phenomenological measurements of age-associated oxidative stress, interspecies comparisons, dietary restriction, and the ongoing elucidation of the role of active oxygen in biology.
Journal ArticleDOI
Effects of a combination of beta carotene and vitamin a on lung cancer and cardiovascular disease
Gilbert S. Omenn,Gary E. Goodman,Gary E. Goodman,Mark D. Thornquist,John R. Balmes,Mark R. Cullen,Andrew G. Glass,James P. Keogh,Frank L. Meyskens,Barbara Valanis,James H. Williams,Scott Barnhart,Scott Barnhart,Samuel P. Hammar +13 more
TL;DR: After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.
Journal ArticleDOI
MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial.
TL;DR: Direct evidence is provided that cholesterol-lowering therapy is beneficial for people with diabetes even if they do not already have manifest coronary disease or high cholesterol concentrations and statin therapy should now be considered routinely for all diabetic patients at sufficiently high risk of major vascular events, irrespective of their initial cholesterol concentrations.
Journal ArticleDOI
Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: Systematic review and meta-analysis
TL;DR: Treatment with beta carotene, vitamin A, vitamin E, and vitamin E may increase mortality and the potential roles of vitamin C and selenium on mortality need further study.
Journal ArticleDOI
The Biologic Clock: The Mitochondria?
TL;DR: The author suggests that the maximal life span of a given mammalian species is largely an expression of genetic control over the rate of oxygen utilization, the rate increasing with the rates of oxygen consumption, which ultimately causes death.