Old fat tissue became partly younger after transplantation into young mice, according to its own aging clocks
Old fat tissue became partly younger after transplantation into young mice, according to its own aging clocks
On September 30, 2026, Vadim Gladyshev’s laboratory at Harvard Medical School posted a preprint on subcutaneous fat transplantation between young and old male mice. For the first time, the researchers measured the biological age of the same tissue before and after surgery. Fat from old mice became younger in young recipients, while fat from young mice aged in old recipients. The findings point to an unexpected mechanism for tissue heat production involving muscle genes, whose causal role in lifespan was confirmed in flies.
Scientists have long suspected that exposure to a young body can rejuvenate old tissues. Over the years, experiments connecting the circulatory systems of old and young animals have shown improvements in muscle, liver, heart, and brain. Yet few studies measured an organ’s age before the intervention. Most simply compared old and young animals at the end of the experiment, a comparison that cannot distinguish actual rejuvenation from slower tissue aging.
To address this gap, the researchers chose subcutaneous fat, which can be collected from a living donor, assessed for biological age, and assessed again ten weeks after transplantation. They tested four donor–recipient combinations: old to young, young to old, young to young, and old to old. Epigenetic and transcriptomic aging clocks, which estimate tissue age from DNA marks and gene activity, gave a consistent result: fat from old mice became younger in young recipients, while fat from young mice aged rapidly in old recipients, reaching the age of the recipients’ own old fat. Tissue also aged in the control pairs: the surgical injury itself caused fibrosis, or tissue scarring, regardless of the donor.
To rule out an apparent effect caused by immune cells entering from the young recipient, the researchers measured gene activity in 165 thousand tissue nuclei. The rejuvenation occurred in the donor’s mature fat cells.
The mechanism was unexpected. The usual markers of brown fat, a tissue that burns fat to generate heat through the protein UCP1, remained unchanged. Instead, the muscle pump SERCA1, which is atypical of fat cells, was activated along with a set of other muscle genes. The authors propose that this futile calcium cycling heats the tissue, as it does in a related type of fat cell. This was the first time it had been linked to a reversal of tissue age. DNA repair was also activated, and lipid droplets became smaller and more uniform, resembling those in young cells. The authors propose this change in lipid droplets as a new indicator of tissue age.
The researchers tested whether these genes causally affect lifespan in Drosophila, the fruit fly commonly used in longevity research, by suppressing two of them in its fat body. Suppressing Lrmda, whose activity decreased during rejuvenation, extended female lifespan. Suppressing SERCA, whose activity increased during rejuvenation, sharply shortened lifespan in both sexes. Continuous SERCA overexpression became harmful over time, whereas scheduled intermittent overexpression extended lifespan in both sexes. Thus, the timing of increased activity of a single gene determined whether its effect was beneficial or harmful.
The effect was confined to the graft, and rejuvenation was incomplete even there: mitochondria in the rejuvenated cells retained their aged shape. The recipient’s own fat tissue, liver, and blood changed little. Transplanted young fat did not restore the old body to health, and transplanted old fat did not age the young body. Rejuvenation of the transplanted tissue therefore remained a local effect rather than rejuvenating the organism as a whole. The same laboratory had previously reported a similarly localized effect in the heart: the graft’s age shifted toward that of its new host, while the recipient’s own heart and blood remained unchanged.