Researchers continue to investigate the effects of branched-chain amino acids (BCAA) on life span in laboratory animals: "Identification of strategies mimicking key [calorie restriction (CR)] mechanisms - increased mitochondrial respiration and reduced production of oxygen radicals - is a hot topic in gerontology. Dietary supplementation with essential and/or branched chain amino acids (BCAAs) exerts a variety of beneficial effects in experimental animals and humans and has been recently demonstrated to support cardiac and skeletal muscle mitochondrial biogenesis, prevent oxidative damage, and enhance physical endurance in middle-aged mice, resulting in prolonged survival. ... A body of recent evidence suggest that amino acids, and in particular BCAAs, behave as evolutionary conserved modulators of lifespan of different organisms ... [Like exercise, BCAA supplementation] does not affect maximum lifespan, but increases the median lifespan, an indicator that specific diseases have been prevented. ... A broad range of questions await answers. The first point to be clarified is the role that specific amino acid signatures can play, directly or indirectly, in the CR effects on healthspan. ... there is need to investigate which amino acid (or specific amino acid combination) is required for the beneficial effects seen in mammals. Not last in importance, large, randomized clinical trials are necessary to assess the safety and efficacy of BCAA/amino acid supplementation for the prevention and treatment of the disabling consequences of energy depletion in the elderly."