Polyphenols as Caloric Restriction Mimetics Regulating Mitochondrial Biogenesis and Mitophagy

The tight coordination between mitochondrial biogenesis and mitophagy can be dysregulated during aging, critically influencing whole-body metabolism, health, and lifespan. To date, caloric restriction (CR) appears to be the most effective intervention strategy to improve mitochondrial turnover in aging organisms. The development of pharmacological mimetics of CR has gained attention as an attractive and potentially feasible approach to mimic the CR phenotype. Polyphenols, ubiquitously present in fruits and vegetables, have emerged as well-tolerated CR mimetics that target mitochondrial turnover. Here, we discuss the molecular mechanisms that orchestrate mitochondrial biogenesis and mitophagy, and we summarize the current knowledge of how CR promotes mitochondrial maintenance and to what extent different polyphenols may mimic CR and coordinate mitochondrial biogenesis and clearance. The maintenance of functional mitochondria is critical during development as well as throughout life. The slowdown of mitochondrial turnover associated with aging has been shown to contribute to the pathogenesis of age-related diseases.Caloric restriction is a well-known intervention that has been shown to ameliorate mitochondrial biogenesis and mitophagy, thereby attenuating age-related decline in mitochondrial function. However, the strict and life-long compliance with this dietary regimen has promoted the investigation of compounds with caloric restriction mimetic properties.Plant polyphenols may represent an attractive source of caloric restriction mimetics. Recent research has confirmed that these compounds may partly mimic the beneficial effects of caloric restriction, inducing molecular mechanisms that govern mitochondrial biogenesis and mitophagy.