Boosting Cellular Longevity Through Intracellular ATP Modulation

Abstract

Aging results from the gradual accumulation of molecular damage as a result of cellular processes and is characterized by impaired functions, most notably an age-related decline in ATP production. However, the causal relationship between cellular ATP homeostasis and aging has not been established. In this study, we employed a nucleotide transporter from a eukaryotic intracellular parasite to directly alter ATP levels in budding yeast cells and exchange it with the extracellular milieu. We found that ATP depletion significantly shortens lifespan, whereas supplementation of the medium with ATP fully restores it. Analysis of gene expression showed inhibition of catabolic processes suggesting that increased ATP suppresses glucose metabolism. Our results also showed that ATP supplementation leads to lifespan extension. Overall, our study revealed the direct impact of cellular ATP homeostasis on the regulation of lifespan. This work offers new insights into the bioenergetic control of aging and positions energy metabolism as a promising target for longevity interventions.