Caloric restriction and exercise "mimetics'': Ready for prime time?

Abstract

Exercise and diet are powerful interventions to prevent and ameliorate various pathologies. The development of pharmacological agents that confer exercise- or caloric restriction-like phenotypic effects is thus an appealing therapeutic strategy in diseases or even when used as life-style and longevity drugs. Such so-called exercise or caloric restriction "mimetics" have so far mostly been described in pre-clinical, experimental settings with limited translation into humans. Interestingly, many of these compounds activate related signaling pathways, most often postulated to act on the common downstream effector peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle. In this review, resveratrol and other exercise- and caloric restriction "mimetics" are discussed with a special focus on feasibility, chances and limitations of using such compounds in patients as well as in healthy individuals.

Keywords: (−)-Epicatechin (PubChem CID 72276); AICAR (PubChem CID 266934); AMPK; Caloric restriction; Celastrol (PubChem CID 122724); Diet; Exercise; GSK4716 (PubChem CID 5399376); GW1516 (PubChem ID 9803963); Metformin (PubChem CID 4091); Mimetics; Nicotinamide riboside (PubChem CID 439924); PGC-1α; PPARβ/δ; Rapamycin (PubChem CID 5040); Resveratrol; Resveratrol (PubChem CID 445154); SR9009 (PubChem ID 57394020); SRT1720 (PubChem ID 25232708); Skeletal muscle; Ursolic acid (PubChem CID 64945).