FGF21 Hormone Rejuvenates Aged Human Stem Cells by Boosting Autophagy

A new study demonstrates that the metabolic hormone FGF21 can rejuvenate aged human adipose-derived mesenchymal stem cells (MSCs) through enhanced autophagy—the cellular "housekeeping" process that clears damaged components. Using human cells rather than just animal models makes this finding particularly relevant. The researchers found that FGF21 activates a transcription factor called TFE3, which ramps up autophagy flux in aged stem cells. This intervention restored functional characteristics that had declined with age, essentially making old stem cells behave more like young ones. FGF21 has gained attention in longevity research because it increases during fasting and exercise, and supplementation extends lifespan in mice. This work reveals a specific mechanism—autophagy enhancement—through which it may exert rejuvenating effects. For human applications, this matters because mesenchymal stem cells are already used therapeutically, but their effectiveness declines with donor age. If FGF21 or related interventions can restore aged stem cell function, it could improve regenerative medicine outcomes in older patients. The autophagy connection also aligns with other longevity interventions like rapamycin and spermidine.