Broad Effects of Activation of Alcohol Dehydrogenase 1 on Healthspan Extension

Summary Nutritional, genetic, and pharmacological interventions can extend lifespan; however, fewer have been shown to extend healthspan—the period of life free from chronic, debilitating diseases. In line with this, the molecular effectors that drive healthspan are even less understood than those responsible for lifespan extension. We recently reported that activation of Alcohol Dehydrogenase 1 (ADH-1) extends lifespan in yeast and C. elegans . In addition, adh-1 is transcriptionally activated in yeast, worms, mice, and humans in response to caloric restriction—an intervention that extends not only lifespan but also healthspan. Therefore, we investigated whether activating adh-1 could also extend healthspan. We demonstrate here that adh-1 activation has broad and robust effects on health, including resistance to age-related obesity, delayed sarcopenia, and attenuated neurodegeneration. Mechanistically, ADH-1-driven healthspan extension is associated with improved proteostasis. These findings position ADH-1 as a promising target for future research aimed at promoting healthy aging.