Ageing & Sports

Abstract

Increasing life expectancy has resulted in a growing number of individuals living with chronic, age-related conditions. This challenges healthcare systems worldwide and results in loss of quality of life in individuals living with chronic conditions. Strategies to promote healthy aging are thus gaining attention. Lifestyle factors such as caloric restriction, carbohydrate restriction and physical activity specifically modify a number of biological pathways associated with aging. One central shared mechanism seems to be the upregulating of maintenance pathways such as the AMPK signaling pathway, triggered by a low cellular energy status, as well as downregulation of anabolic pathways such as the insulin/IGF-1 signaling pathway. The transient energy deficit evoked by (intermittent) caloric restriction or vigorous physical activity or the phenotypic imitation of this physiological state by dietary carbohydrate restriction might offer some biologic plausibility for the observation of the benefits of these lifestyle factors. Largely independent of these mechanisms, physical activity directly impacts on downstream adaptive cellular responses via muscle-tissue crosstalk through myokines, i.e. hormone-like substances secreted by skeletal muscle in response to exercise. It is worth noting that distinct pharmaceuticals such as metformin, SGLT2-inhibitors and statins have the potential to complement lifestyle factors by directly modifying these longevity-associated pathways. Lifestyle factors are relevant determinants of health- and potentially of lifespan. Recent findings have significantly advanced our understanding of the mechanisms involved. This narrative review provides a perspective on selected modifiable determinants of healthspan and furthermore elucidates therapeutic avenues that have the potential to attenuate premature aging and to refine personalized preventive care.Key Words: Caloric Restriction, Exercise, Ketosis, -Hydroxybutyrate, Nutrient Sensing Pathways, AMPK, Insulin, IGF-1, mTOR, Metformin, SGLT2i, Statins