Exercise preserves physical fitness during aging through AMPK and mitochondrial dynamics

Abstract

Exercise is a nonpharmacological intervention that improves health during aging and a valuable tool in the diagnostics of aging-related diseases. In muscle, exercise transiently alters mitochondrial functionality and metabolism. Mitochondrial fission and fusion are critical effectors of mitochondrial plasticity, which allows a fine-tuned regulation of organelle connectiveness, size, and function. Here we have investigated the role of mitochondrial dynamics during exercise in the model organism Caenorhabditis elegans . We show that in body-wall muscle, a single exercise session induces a cycle of mitochondrial fragmentation followed by fusion after a recovery period, and that daily exercise sessions delay the mitochondrial fragmentation and physical fitness decline that occur with aging. Maintenance of proper mitochondrial dynamics is essential for physical fitness, its enhancement by exercise training, and exercise-induced remodeling of the proteome. Surprisingly, among the long-lived genotypes we analyzed ( isp-1 , nuo-6 , daf-2 , eat-2 , and CA-AAK-2 ), constitutive activation of AMP-activated protein kinase (AMPK) uniquely preserves physical fitness during aging, a benefit that is abolished by impairment of mitochondrial fission or fusion. AMPK is also required for physical fitness to be enhanced by exercise, with our findings together suggesting that exercise may enhance muscle function through AMPK regulation of mitochondrial dynamics. Our results indicate that mitochondrial connectivity and the mitochondrial dynamics cycle are essential for maintaining physical fitness and exercise responsiveness during aging and suggest that AMPK activation may recapitulate some exercise benefits. Targeting mechanisms to optimize mitochondrial fission and fusion, as well as AMPK activation, may represent promising strategies for promoting muscle function during aging.

Overexpression of mitochondrial fusion genes enhances resilience and extends longevity

“…We tested for nematode resistance to death by bacterial colonization of the intestine. The slow kill assay was performed as previously described [61, 62]. OP50 bacteria was seeded to the center of NGM plates containing 100 mg/L FUdR and plates were left at room temperature for two days.…”

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

“…Regular physical activity and dietary restriction are the most effective approaches to preserve mitochondrial dynamics through AMPK activation during aging (Campos et al., 2023; Weir et al., 2017). Another well‐characterized experimental paradigm to delay aging and promote lifespan extension is mitochondrial transplantation.…”

“…Other strategies for modulating the nutrient‐sensing network for healthspan improvement include dietary interventions such as CR and fasting, as well as exercise combined with balanced nutrition (Campos et al., 2023). As previously discussed in this review, optimizing the diet in combination with exercise may be beneficial for addressing several of the hallmarks of aging (V. D. Longo & Anderson, 2022; Longo et al., 2021).…”

Exercise to Promote Healthy Mitochondria and Improve Lifestyle of Aging Society

“…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]. Exercise in the elderly has also been reported to improve mitochondrial efficiency as observed with the increase in Ser637 phosphorylation in Drp1 [12].…”