Exercise and mitochondrial remodeling to prevent age-related neurodegeneration

Abstract

Healthy brain activity requires precise ion and energy management creating a strong reliance on mitochondrial function. Age-related neurodegeneration leads to a decline in mitochondrial function and increased oxidative stress, with associated declines in mitochondrial mass, respiration capacity, and respiration efficiency. The interdependent processes of mitochondrial protein turnover and mitochondrial dynamics, known together as mitochondrial remodeling, play essential roles in mitochondrial health and therefore brain function. This mini-review describes the role of mitochondria in neurodegeneration and brain health, current practices for assessing both aspects of mitochondrial remodeling, and how exercise mitigates the adverse effects of aging in the brain. Exercise training elicits functional adaptations to improve brain health, and current literature strongly suggests that mitochondrial remodeling plays a vital role in these positive adaptations. Despite substantial implications that the two aspects of mitochondrial remodeling are interdependent, very few investigations have simultaneously measured mitochondrial dynamics and protein synthesis. An improved understanding of the partnership between mitochondrial protein turnover and mitochondrial dynamics will provide a better understanding of their role in both brain health and disease, as well as how they induce protection following exercise.

Mitochondrial calcium uniporter deficiency in dentate granule cells remodels neuronal metabolism and impairs reversal learning

“…Mitochondria are dynamic organelles that may change their number, shape, localization, structure, proteome, and genome, in response to intrinsic, cytosolic, or nuclear signals (Gottlieb & Bernstein, 2016). This multilevel regulation of mitochondrial function allows the remodeling of cellular metabolism in connection to cellular workload, cell signaling, and several physio‐pathological states (Gan et al, 2018; Motori et al, 2020; O'Reilly et al, 2022; Rajab et al, 2022; Rastogi et al, 2019).…”

“…This multilevel regulation of mitochondrial function allows the remodeling of cellular metabolism in connection to cellular workload, cell signaling, and several physio-pathological states (Gan et al, 2018;Motori et al, 2020;O'Reilly et al, 2022;Rajab et al, 2022;Rastogi et al, 2019).…”

How can we modulate aging through nutrition and physical exercise? An epigenetic approach

“…O’Reilley and colleagues reviewed how physical activity relates with mitochondrial remodelling and how these, in turn, influence neurodegeneration. They highlighted how mitochondrial function strongly benefits from aerobic exercise in some tissues, and that this may positively impact the brain by delaying the age-associated increase of oxidative stress that leads to mitochondrial decline [ 204 ]. Furthermore, a review by Reddy et al explores the “exercise responsome” and several molecules (exerkines) which are released during physical activity (such as Cathepsin B, Adiponectin, Osteocalcin and FGF21) [ 205 , 206 ].…”

Exercise to Promote Healthy Mitochondria and Improve Lifestyle of Aging Society

“…During aging, mitochondrial performance declines as the balance between fusion and fission is often compromised [5,6]. This imbalance has been implicated in neurodegenerative diseases [6], sarcopenic muscles [2] and various other pathological conditions [2,4].…”

“…During aging, mitochondrial performance declines as the balance between fusion and fission is often compromised [5,6]. This imbalance has been implicated in neurodegenerative diseases [6], sarcopenic muscles [2] and various other pathological conditions [2,4]. Exercise has been reported to increase mitochondrial biogenesis, remove damaged mitochondria, stimulate mitochondrial function [5,7] and delay aging associated decline in physical fitness [8][9][10] and cognitive function [11].…”