As people age, their immune systems deteriorate. This makes them more susceptible to infections, and can mean that vaccines are less effective.
This new research shows that immune cells in older people have damaged DNA, a hallmark of ageing. Targeting this DNA damage could be a key way to rejuvenate immune systems in older people and therefore increase healthspan.
mTOR inhibitors, such as rapamycin, are drugs which target an important enzyme in cells called mTOR which becomes more active during ageing. Such drugs have been shown to increase lifespan in many organisms including yeast, flies and mice. They also improve immune responses to vaccination in older people. Dr Loren Kell, with Professors Ghada Alsaleh, Lynne Cox, and Katja Simon, hypothesised that rapamycin could be used to directly alleviate DNA damage.
To test this, the group exposed human T cells in the lab to a DNA-damaging agent that killed 80% of the cells after 24 hours. If cells were instead treated with rapamycin at the same time as exposure to DNA damage, 60% were still alive at 24 hours – 3 times more than without rapamycin. The presence of rapamycin appeared to reduce the DNA damage in the T cells. Professor Cox said “The cells showed less DNA damage even after only 4 hours – it’s a very fast response. We don’t yet know whether rapamycin is blocking damage formation or helping cells to repair the damage more quickly and efficiently, so this research opens up a whole new area of study to identify the mechanism of protection”.