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Longevity Briefs: Targeting The Biology Of Ageing To Boost The Immune System

Posted on 16 June 2021

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Mechanistic target of rapamycin (mTOR) is a signalling molecule that is thought to play an important role in the ageing process, controlling how cells distribute their energy between energy-saving and energy-demanding processes. Inhibiting mTOR extends lifespan in animal models and improves the function of various organ systems, including the immune system. Inhibition of mTOR appears to enhance the effects of interferons – molecules that are released by cells and which increase the expression of antiviral genes. Drugs which inhibit mTOR might therefore protect against viral infections such as COVID-19.

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Interferons are released by cells that are infected a virus. These interferons then signal to neighbouring cells to increase their own antiviral defences, helps them commit suicide (apoptosis) if they are infected, and activates cells of the immune system.

What did the researchers do: In a series of double-blind, randomised, placebo-controlled trials in adults aged 65 and above, researchers studied whether RTB101, an mTOR inhibitor, could reduce the incidence of respiratory tract infections. The phase 2 trial included 652 participants, while the phase 3 trial included 1024 participants.

Key takeaway(s) from this research: Low doses of RTB101 were well tolerated and safe, and were found to upregulate interferon-induced antiviral responses in older adults. However, the effects of RTB101 on respiratory tract infections were not consistent: the phase 2 trial showed reduced incidence in the treatment group, while the phase 3 trial did not. This may be related to differences in how respiratory tract infections were reported and measured: the phase 2 trial examined laboratory-confirmed infections, whereas the phase 3 trial examined respiratory symptoms consistent with a respiratory tract infection, without laboratory confirmation.

Despite the inconclusive results, these studies are encouraging. They suggest that we can safely target the biology of ageing in older adults, and that such interventions improve at least some aspects of the function of ageing organ systems (in this case the antiviral response induced by interferons).

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    Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials:

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