These findings demonstrate that OT+A5i has a significant ability to extend health span and highlight the sex-specific differences in aging and in responses to longevity treatments.
A new study featured in the journal Aging has found that combining oxytocin with an Alk5 inhibitor (OT+A5i) can greatly improve both lifespan and healthspan in older, frail male mice. The research, led by first author Cameron Kato and corresponding author Irina M. Conboy, an Aging-US Editorial Board Member from the University of California, Berkeley, showed that this treatment offered significant rejuvenating effects in males but not in females, suggesting that biological differences between the sexes may play a crucial role in how aging therapies work.
The research team explored a two-drug strategy aimed at addressing key biological changes that occur with age. Oxytocin, a hormone that naturally decreases over time and supports tissue regeneration, was paired with an Alk5 inhibitor, a compound that suppresses the TGF-beta pathway. This pathway becomes excessively active as organisms age, fueling chronic inflammation and tissue degradation. In the experiment, frail mice at 25 months old (about 75 years in human terms) received regular doses of the OT+A5i combination.
Dramatic Longevity and Performance Gains
Male mice treated with the therapy lived more than 70% longer than untreated controls and showed noticeable improvements in physical strength, agility, and memory. Based on hazard ratio analysis, treated males were almost three times less likely to die at any point compared with those that did not receive the therapy.
"Treatment of old frail male mice with OT+A5i resulted in a remarkable 73% life extension from that time, and a 14% increase in the overall median lifespan."
The therapy also reduced "biological noise" in circulating blood proteins -- an established marker of aging -- bringing those levels back to a more youthful state. Short-term benefits were seen in both sexes; however, after four months of continuous treatment, only the male mice showed sustained improvement in systemic protein balance. Female mice did not experience significant gains in lifespan or healthspan, though middle-aged females did show improved fertility after treatment.
These results underscore the importance of understanding sex-specific biology when developing treatments for aging. While the reasons for these differences remain unclear, the findings provide a new model for studying and designing longevity therapies.
Oxytocin is already FDA-approved, and Alk5 inhibitors are currently in clinical trials, suggesting that this approach could be translated to humans. With strong results in aged and frail male animals, OT+A5i appears to be a promising candidate for improving late-life health and survival.
Reference: "Sex-specific longitudinal reversal of aging in old frail mice" by Cameron Kato, Jessica Zheng, Cindy Quang, Sophia Siopack, Joana Cruz, Zachery R. Robinson, Nicole Fong, Zhixin A. Zhang, Patrick Young, Michael J. Conboy and Irina M. Conboy, 21 August 2025, Aging.
DOI: 10.18632/aging.206304
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