Pleiotropic and multi-systemic actions of physical exercise on PGC-1a signaling during the aging process

Physical training is a potent therapeutic approach for improving mitochondrial health through peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1a) signaling pathways. However, compre-hensive information regarding the physical training impact on PGC-1a in the different physiological systems with advancing age is not fully understood. This review sheds light on the frontier-of-knowledge data regarding the chronic effects of exercise on the PGC-1a signaling pathways in rodents and humans. We address the molecular mechanisms involved in the different tissues, clarifying the precise biological action of PGC-1a, restricted to the aged cell type. Distinct exercise protocols (short and long-term) and modalities (aerobic and resistance exercise) increase the transcriptional and translational PGC-1a levels in adipose tissue, brain, heart, liver, and skeletal muscle in animal models, suggesting that this versatile molecule induces pleiotropic responses. However, PGC-1a function in some human tissues (adipose tissue, heart, and brain) remains challenging for further investigations. PGC-1a is not a simple transcriptional coactivator but supports a biochemical environment of mitochondrial dynamics, controlling physiological processes (primary metabolism, tissue remodeling, autophagy, inflamma-tion, and redox balance). Acting as an adaptive mechanism, the long-term effects of PGC-1a following exercise may reflect the energy demand to coordinate multiple organs and contribute to cellular longevity.

Automated summary

Physical training can improve mitochondrial health through PGC-1a signaling pathways. However, the impact of physical training on PGC-1a in different physiological systems with advancing age is not well understood. This review provides comprehensive information on the effects of exercise on PGC-1a signaling pathways in rodents and humans, addressing molecular mechanisms and highlighting the importance of further investigation in certain human tissues. PGC-1a functions as more than a transcriptional coactivator, playing a role in mitochondrial dynamics and various physiological processes.