Age-associated decline of Coenzyme A leads to intestinal stem cells dysfunction via disturbing iron homeostasis

The decline in adult stem cell performance is closely linked to tissue malfunction and the rising incidence of age-related diseases. To investigate the molecular basis of these impairments, our screening strategy identified reduced activity in the pantothenate/coenzyme A (CoA) pathway within aged ISCs. Furthermore, exogenous CoA supplementation restructured ISC metabolic pathways, reversing age-induced hyperproliferation and intestinal dysfunction, and thus extending Drosophila lifespan by curbing excessive iron accumulation in ISCs. These findings uncover a new mechanism of stem cell aging and propose that pantothenate and CoA could be potential therapeutic targets for treating age-related diseases and enhancing healthy aging in humans. In our study, we explored the connection between the aging of adult stem cells and the rise of age-related diseases, uncovering a significant metabolic link. As stem cells age, a key metabolic pathway involving pantothenate and CoA becomes less active, leading to an accumulation of excess iron, which disrupts cellular function and contributes to the aging process. To counteract this decline, we added pantothenate and CoA to the aging stem cells, restoring their normal function, reducing iron buildup, and ultimately improving the health and lifespan of old fruit flies. This simple intervention not only highlights the potential of pantothenate and CoA as powerful tools to combat the effects of aging but also suggests broader implications for treating age-related diseases and promoting healthy aging in humans. Our findings provide a new perspective on the biology of aging and open up exciting new avenues for therapeutic interventions that could improve the quality of life for older individuals.