Let’s initiate trials of potential geroprotective therapies

Dr Lynne Cox explains the importance of geroprotectors – especially during COVID-19.

This month The Lancet launches its own journal on Longevity, publishing clinically-focused Longevity and healthy aging research and review. In the first edition, Lynne Cox, Ilaria Bellantuono, Janet Lord, Elizabeth Sapey, Joan Mannick, Linda Partridge, et al., have published a commentary calling for use of geroprotectors in clinical trials in older people especially in the context of COVID protection. We spoke to Dr Cox to find out more.

Longevity.Technology: We are delighted the The Lancet has launched Healthy Longevity, increasing the spotlight on geroscience and the need to improve lifespan and healthspan. Its remit is to “encompass early-stage clinical research into the mechanisms of ageing through to epidemiological and societal research on changing populations, including clinical trials in all disciplines focused on older people, gerontological science, and age-specific clinical guidelines,” as well as publishing “clinical and policy reviews which aim to shape and contextualise the debate on this fast-growing discipline.” We very much look forward to its impact on this field.

The COVID-19 pandemic has highlighted that a geroscience approach, targeting aging processes to prevent multimorbidity, is key to improving healthspan, lifespan and disease outcomes. Initiating clinical trials of potential geroprotective therapies would not only help guard against future pandemics, but begin to address the needs of an aging population. By understanding and targeting the biology of aging, diseases of aging can be delayed, cured, or even prevented entirely.

Dr Lynne Cox is Associate Professor in Biochemistry at the University of Oxford where she studies the molecular basis of human aging, with the aim of reducing the morbidity and frailty associated with old age.

She told Longevity.Technology that aging is not just accompanied by an increased risk of chronic health conditions, but also infectious diseases, and nowhere is this more obvious than in the COVID-19 death statistics, with mortality rising gradually with age until the late 60s, then accelerating so that people over 80 years old are at “greatly elevated risk”.

“In order to protect this most vulnerable population group from COVID, we need to address the reason they are so vulnerable,” she says “and that is likely in a large part to be due to age-associated decreases in immune responses, or immunosenescence.

“Vaccination alone may not protect the very old and frail, as the same immunosenescence that makes them susceptible to COVID-19 means they are unlikely to respond robustly to immunisation. Yet the UK government has published plans to first vaccinate the very old, in gradually decreasing age cohorts [1] – even though the bulk of vaccine trials so far study healthy people under 65 years.”

The Oxford-Astra Zeneca vaccine study is a notable exception, however, with Phase 2 trials in older people.

“Geroscience has a major role to play during a pandemic that hits predominantly older people the hardest.”

Dr Cox says it’s critical that we start using therapeutics shown to be effective through geroscience studies to improve the health and resilience of older people to infectious and other diseases. This need is the driving force behind the piece in The Lancet.

“We have come together as an international group of geroscientists and clinicians to call for older people, even those with significant pre-existing health conditions,” explains Dr Cox “to be included in clinical trials, and in particular for the rapid deployment of geroprotective drugs with good safety profiles that have already shown promise in older people with respiratory tract infections – drugs such as mTOR inhibitors, statins and metformin.

“There is also likely to be a role for senolytic drugs that selectively kill senescent cells in treating ‘long COVID’, particularly dealing with the lung fibrosis that appears to be a key pathological feature of COVID-19. Geroscience has a major role to play during a pandemic that hits predominantly older people the hardest.”

Read the piece by Dr Lynne Cox et al. in The Lancet Healthy Longevity here.
[1] https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-25-september-2020/jcvi-updated-interim-advice-on-priority-groups-for-covid-19-vaccination

Image courtesy of Lynne Cox