Exercise Mimetics in Aging: Suggestions from a Systematic Review

Abstract

Background/Objectives: Growth in the aging world population is accompanied by an increase in comorbidities, profoundly impacting the quality of life of older people. This development has motivated a large effort to investigate the mechanisms underlying aging and the search for countermeasures. The most investigated strategies envisage the control of diet and physical exercise, which exploit both common and distinct mechanisms to promote health. Since the application of nutritional and exercise protocols to aged persons introduces several issues due to their disabled state, some strategies have been developed. The nutritional approach exploits a wide range of compounds, including calorie restriction mimetics, supplements, antioxidants, and others. In the context of exercise, in recent years, molecules able to provide similar effects to exercise, the so-called exercise mimetics, have been developed. Methods: To have a better perspective on exercise mimetics and their connection with nutrition, we performed a systematic search of the PubMed and Scopus databases using the term "exercise mimetics". Results: In total, 97 research articles were selected and discussed. The present review provides evidence of the presence of multiple exercise-mimetic compounds and physical strategies that can target metabolic pathways, oxidative stress defense mechanisms, or myokine modulation. Conclusions: Interestingly, this review highlights that an important number of exercise mimetics are represented by products of natural origin and supplements assimilable with diet. This evidence provides a further link between exercise and nutrition and confers a central role on nutrition in the context of exercise mimetics.

Keywords: aging; exercise; exercise mimetics; health span; lifespan; metabolism; myokines; natural compounds; nutrient sensing pathway.

Figure 1

PRISMA flow diagram of the systematic search (https://creativecommons.org/licenses/by/4.0/ accessed on 9 March 2025).

Figure 2

Diagrammatic representation of sirtuins and AMPK downstream interactors. Abbreviations: AMPK (AMP-activated protein kinase), SIRT (sirtuin), PGC1 (peroxisome proliferator-activated receptor γ coactivator), PPARs (peroxisome proliferator-activated receptor γ), RXR (retinoid X receptor), ERRs (estrogen-related receptors), NRF1/2 (nuclear factor E2-related factor 1/2).