Medications against aging pose long-term health risks Good quality long-term research is needed to confirm their safety

There are many medications in development aimed at combating aging and old age-related diseases, targeting specific aspects of the body. According to Marcel Olde Rikkert, geriatrician at Radboud university medical center, these may show effects in the short term, but there is a risk of disrupting balance and side effects in the long run. Together with colleagues from the US and Canada, he has made recommendations in Nature Aging to improve research on anti-aging treatments.

Medications that rejuvenate dying body cells (i.e. ‘senescent cells’), boost the immune system, or repair DNA damage may sound like a good strategy to keep the elderly young. However, this is more nuanced, according to geriatrician Marcel Olde Rikkert: 'Such treatments focus on just a small detail in the body and fail to consider the person as a whole. In the long term, they could disturb the body’s physiological balance and result in more harmful consequences than any short-term benefits.'

Many such negative effects have already been observed with various drug treatments. For example, doxorubicin, a cancer drug, causes heart damage after prolonged use. Severely ill patients receiving parenteral nutrition to prevent further weight loss may die sooner. And taking excessive antioxidants, such as vitamin E and beta-carotene, has been shown to later increase the risk of death.

Balance

'As researchers, we sometimes think we know better than the body's natural response to stressors, for example, infectious pathogens. But that response has been shaped by a very long process of evolution', says Olde Rikkert. 'The body is complex and maintains a balance, for instance, between growth and maintenance, reproduction and repair, and independence and dependence or organ systems. It’s often not a good idea to disrupt that repair balance by artificially normalizing biomarkers too quickly.'

This was evident, for instance, in a study on the retina. As we age, more cells in the retina stop functioning optimally and cease dividing. Administering drugs that lowered so-called complement factors in the blood kept these senescent retinal cells alive longer. However, this did not improve vision but led to further deterioration. 'The dying cells turned out to be harmful to the surrounding cells, and the body needs the opportunity to clear out these extremely aged cells. The larger context was not sufficiently considered here.'

Exercise

Olde Rikkert emphasizes that aging is a natural process that also serves as a protective mechanism against certain diseases and thus has its benefits. 'As you get older, cells may enter a resting state. Stem cells, the type of cells in the body that can still perform all functions, thus gradually become depleted. And our telomeres, structures at the ends of chromosomes, shorten over time. While this may seem negative, it partially prevents uncontrolled cell growth, and thus the development of cancer.'
Rather than combating aging itself, Olde Rikkert advocates for preserving health. The most important factor is a healthy lifestyle. 'Things like good nutrition and exercise affect the body as a whole, not just a single part. We see that the Tsimane people in Bolivia hardly suffer from age-related diseases like those in Western countries, such as diabetes, Alzheimer’s, and cardiovascular diseases. This shows that lifestyle effects outweigh general biological aging effects.'

Long-Term Measurements

Young people who already use anti-aging treatments should be cautious, warns Olde Rikkert. 'These are often individuals who are already focused on health and pursuing a healthy lifestyle. Such treatments likely have little or no positive effect in the short term, while there is a risk of negative consequences in the long term. We don’t yet know these risks simply because we haven’t measured for long enough.' These risks could include increased cancer or infection rates.

One of the researchers’ recommendations to reduce the risks of anti-aging treatments is long-term, extensive monitoring, ideally for several decades. Preferably, this would be in comparison with a healthy lifestyle, with exercise as a key component. It would be wise to start with the oldest population and gradually work back to younger individuals. Maintaining health and a healthy lifestyle remains crucial in the fight against aging.

About the publication

These recommendations were published in Nature Aging: Balancing the promise and risks of geroscience interventions. Authors: Alan A. Cohen, John R. Beard, Luigi Ferrucci, Tamàs Fülöp, Vadim N. Gladyshev, Mahdi Moqri, Marcel G.M. Olde Rikkert, Martin Picard. DOI: 10.1038/s43587-024-00788-9

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