New Insights Into The Role Of Mitochondria In Aging [See: https://thinksteroids.com/community/threads/134303550 ]
The mitochondrial theory of aging postulates that the lifelong accumulation of somatic mitochondrial DNA (mtDNA) mutations leads to mitochondrial abnormalities resulting in a progressive decline in tissue function. Mitochondrial abnormalities and mtDNA mutagenesis are well-established intrinsic instigators that drive multisystem degeneration, stress intolerance, and energy deficits during aging in humans, monkeys, and rodents. Reduced mitochondrial quality and content in multiple tissues is also implicated in several aging-associated conditions, including cancer, obesity, cardiovascular diseases, hypertension, type 2 diabetes, osteoporosis, and dementia, as well as in the pathogenesis of neurometabolic syndromes, psychiatric disorders, end-stage renal disease, and mitochondrial cytopathies. Current treatment strategies for conditions associated with mitochondrial dysfunction address the secondary symptoms but not the deficiency itself. One possible approach to mitigating the primary deficiency is to boost the residual mitochondrial oxidative capacity by increasing functional mitochondrial mass in the affected tissues.
The epidemic emergence of modern chronic diseases largely stems from the adoption of a sedentary lifestyle and excess energy intake. There is incontrovertible evidence from epidemiologic studies that endurance exercise extends life expectancy and reduces the risk of chronic diseases. Endurance exercise is the most potent physiological inducer of mitochondrial biogenesis in skeletal muscle and also has profound effects on metabolism in various other tissues, including heart, brain, adipose tissue, and liver. These adaptations result in improved healthspan, reduced risk of morbidity and mortality, and enhanced quality of life. In this work, researchers used the mtDNA mutator mouse (designated the PolG mouse), a model of progeroid aging that exhibits elevated mtDNA point mutations and systemic mitochondrial dysfunction and phenocopies human aging, to investigate whether endurance exercise can effectively counteract the entrenched multisystem degeneration and mitochondrial dysfunction to mitigate premature aging in these mice.
Safdar A, Bourgeois JM, Ogborn DI, et al. Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice. Proceedings of the National Academy of Sciences. Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice — PNAS
A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities.
The mitochondrial theory of aging postulates that the lifelong accumulation of somatic mitochondrial DNA (mtDNA) mutations leads to mitochondrial abnormalities resulting in a progressive decline in tissue function. Mitochondrial abnormalities and mtDNA mutagenesis are well-established intrinsic instigators that drive multisystem degeneration, stress intolerance, and energy deficits during aging in humans, monkeys, and rodents. Reduced mitochondrial quality and content in multiple tissues is also implicated in several aging-associated conditions, including cancer, obesity, cardiovascular diseases, hypertension, type 2 diabetes, osteoporosis, and dementia, as well as in the pathogenesis of neurometabolic syndromes, psychiatric disorders, end-stage renal disease, and mitochondrial cytopathies. Current treatment strategies for conditions associated with mitochondrial dysfunction address the secondary symptoms but not the deficiency itself. One possible approach to mitigating the primary deficiency is to boost the residual mitochondrial oxidative capacity by increasing functional mitochondrial mass in the affected tissues.
The epidemic emergence of modern chronic diseases largely stems from the adoption of a sedentary lifestyle and excess energy intake. There is incontrovertible evidence from epidemiologic studies that endurance exercise extends life expectancy and reduces the risk of chronic diseases. Endurance exercise is the most potent physiological inducer of mitochondrial biogenesis in skeletal muscle and also has profound effects on metabolism in various other tissues, including heart, brain, adipose tissue, and liver. These adaptations result in improved healthspan, reduced risk of morbidity and mortality, and enhanced quality of life. In this work, researchers used the mtDNA mutator mouse (designated the PolG mouse), a model of progeroid aging that exhibits elevated mtDNA point mutations and systemic mitochondrial dysfunction and phenocopies human aging, to investigate whether endurance exercise can effectively counteract the entrenched multisystem degeneration and mitochondrial dysfunction to mitigate premature aging in these mice.
Safdar A, Bourgeois JM, Ogborn DI, et al. Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice. Proceedings of the National Academy of Sciences. Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice — PNAS
A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities.