Rapamycin Enhances DNA Damage Resistance in Aging Human Immune Cells

Recent research led by the University of Oxford reveals that low-dose rapamycin acts as a protective agent for the genome in aging human immune cells, significantly reducing DNA damage. This discovery highlights rapamycin's potential role in promoting healthy aging and immune function.

The mechanistic target of rapamycin (mTOR) pathway is a crucial regulator of cell growth, metabolism, and survival, responding to environmental cues like nutrients and stress. As the immune system ages, it accumulates DNA damage which contributes to immunosenescence, the decline in immune function associated with aging. Rapamycin, originally developed to prevent organ rejection by suppressing the immune system, is known to inhibit the mTOR pathway. Interestingly, at doses that do not suppress immune activity, it can mitigate cellular aging processes.

In the study "Rapamycin exerts its geroprotective effects in the aging human immune system by enhancing resilience against DNA damage," researchers combined laboratory experiments, immune cell profiling, and a clinical trial involving older adults. The trial involved nine men aged 65–75, who received 1 mg/day of rapamycin or a placebo for four months. Blood samples were collected at multiple points to analyze immune cells.

The experiments demonstrated that cells exposed to rapamycin showed decreased markers of DNA damage, such as γH2AX, and lowered levels of stress proteins like p53 and p21. These proteins are associated with DNA repair and senescence. Notably, rapamycin also increased autophagy, the cell’s recycling process that helps clear damaged components, thus further protecting the DNA. Cells treated with rapamycin exhibited fewer DNA breaks and higher survival rates after genotoxic stress.

Furthermore, four months of rapamycin treatment led to a decrease in markers of cellular senescence and immune exhaustion, such as KLRG1, NKG2A, and LAG3, while p53 levels increased. The expression of inhibitory markers like PD-1 remained unchanged.

These findings suggest that rapamycin directly fortifies genome integrity in human immune cells, potentially supporting healthy aging, improving recovery from radiation exposure, and protecting against cosmic radiation risks during space travel. The research underscores rapamycin's promise as a geroprotective agent, fostering resilience against age-related genetic deterioration.

Source: https://medicalxpress.com/news/2025-09-rapamycin-linked-dna-resilience-aging.html