A new drug combination has been found to extend lifespan in frail, elderly, male mice by a “remarkable 73 per cent”, according to a new study that sheds more light on sex differences in anti-ageing therapies.
Researchers tested a dual-drug approach targeting two biological pathways that are known to change with age.
They tested oxytocin, which is known to support tissue repair, along with another drug known as OT+A5i, which blocks a key pathway involved in regulating cell growth, differentiation, and death.
The key pathway known as TGF-beta becomes overactive with age, contributing to chronic inflammation and tissue damage.
Researchers tested the drug combo on frail mice at 25 months of age – roughly equivalent to 75 human years.
They found that male mice receiving the therapy lived over 70 per cent longer than untreated controls and showed significant improvements in physical endurance, agility, and memory.
Male mice treated with the drug combination were nearly three times less likely to die at any given time than untreated males, scientists found, according to research published in the journal Ageing-US.
“Treatment of old frail male mice with OT+A5i resulted in a remarkable 73 per cent life extension from that time, and a 14 per cent increase in the overall median lifespan,” researchers wrote.
“Further, these animals had significantly increased healthspan, with improved physical performance, endurance, short term memory, and resilience to mortality,” they added.
Frail mice treated with drug combination appeared youthful (Aging-US (2025))
In comparison, previous studies of the popular anti-ageing drug rampamycin reveal that when measured from the start of the therapy, mice have a 9 to 15 per cent increase in survivorship, researchers say.
“Compared to other established lifespan-extending interventions, Oxytocin+A5i demonstrates unique outcomes, such as significantly (over 70 per cent) increased life expectancy from the start of this therapy in old and frail male mice, and a robust decrease in mortality risk,” they wrote.
The latest study also found that the Oxytocin+A5i treatment reduced chaotic levels of some circulating blood proteins, which are key markers of ageing, bringing their levels back to a more youthful state.
However, after four months of continuous treatment, only male mice showed sustained improvement in these protein levels.
Female mice, researchers found, did not experience significant gains in lifespan or healthspan.
The findings highlight the importance of better understanding sex-specific biology when developing treatments for ageing.
“These findings establish the significant health-span extension capacity of OT+A5i and emphasise the differences in ageing and in response to longevity therapeutics between the sexes,” scientists wrote.
Researchers hope the finding could provide a new model for studying and designing longevity therapies.
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