Illustration of rapamycin (red), a drug that inhibits proteins known as MTOR (blue)
Science Photo Library/Alamy
The anti-aging benefits of rapamycin may be related, at least in part, to its ability to prevent DNA damage in immune cells.
Initially created as an immunosuppressant for organ transplant patients, rapamycin blocks the function of the MTOR protein, which is crucial for cell growth and division. Studies suggest that low doses can extend the lifespan of various organisms, including the mouse, potentially by disrupting processes associated with aging, such as inflammation, intracellular breakdown, and decline in mitochondrial function.
Recent research by Lynn Cox and colleagues at Oxford University has demonstrated that rapamycin also appears to prevent DNA damage in certain types of immune cells. DNA damage is one of the key factors contributing to aging in our immune system, accelerating the aging process throughout the body.
The researchers conducted experiments with human T cells, a type of white blood cell responsible for fighting infections. When T cells were exposed to an antibiotic named zeocin alongside rapamycin, significant DNA damage occurred.
Results showed that rapamycin lowered DNA damage and tripled cell survival rates compared to T cells exposed to zeocin alone.
The researchers found no indication that the observed effects were due to other actions of rapamycin, such as preventing cell failure. “We consistently observe this effect regardless of whether rapamycin is administered prior to, during, or post-injury,” noted team member Ghada Arsare at Oxford University.
The rapid response suggests a direct impact. “The effect is very swift, indicating it influences the DNA damage response and accumulation. The lesions observed last about four hours, so it’s unlikely that there are downstream effects impacting other processes,” explained Cox.
According to Matt Kaeberlein from Washington University in Seattle, the findings support the notion that rapamycin can directly protect DNA, but “this is not the critical mechanism.” Researchers aim to explore rapamycin-induced alterations in RNA and proteins produced in immune cells.
In a separate part of the study, nine men aged 50 to 80 were assigned to receive either 1 milligram of rapamycin or a placebo daily. Blood tests conducted eight weeks later revealed that T cells from men taking rapamycin exhibited less DNA damage. Furthermore, neither group experienced a decrease in overall white blood cell counts, indicating that rapamycin does not negatively impact immune functionality. “Our findings confirm that low doses are safe, which is crucial,” stated Cox.
Mitigating DNA damage in the immune system may provide a pathway for reducing overall aging, according to Cox. Arsare highlighted the potential for rapamycin to be used preventively, such as for astronauts exposed to cosmic radiation.
“Rapamycin is particularly promising in addressing aging-related issues where DNA damage is a significant factor, such as skin aging,” noted Kaeberlein. Referring to a study, he added that local use of rapamycin reduces aging markers in human skin. However, he cautioned against generalizing results to other types of damage, such as radiation, given that Cox’s team used antibiotics to create DNA damage.
Zahida Sultanova from the University of East Anglia emphasized the necessity for trials involving women and individuals across various age groups, as the placebo-controlled experiments were limited to older men. Evidence from non-human animal studies indicates that rapamycin may have sex-specific and age-specific effects.
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Source: www.newscientist.com
