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You may know metformin as a diabetes drug and rapamycin as a cancer drug, but clinical trials are underway to determine their efficacy as anti-ageing supplement s, too. The search for more such potential anti-ageing molecules is on around the world.
A recent study involving mice, worms, and monkeys found that as the animals grew older they had less taurine, an amino sulphonic acid present in animal tissue. The study — titled ‘Taurine deficiency as a driver of ageing’ — further found that with taurine supplements the ageing effects could be reversed, leading to longer, healthier lives.
“And then we looked at humans,” says Vijay K Yadav, Assistant Professor, Columbia University, New York. “We measured taurine and its metabolite levels in 12,000 people to see whether taurine in abundance in the blood of humans correlates with the health of 60-year-old humans.” It was found that those with high taurine levels were healthier in numerous ways, including lower rates of obesity, diabetes and cholesterol.
“This is an exciting phase for ageing interventions. In the next few years, we will have an anti-ageing basket of different molecules as a way forward for precision medicine,” says Yadav.
Researchers are spreading the net far and wide. “Indolepropionamide, resveratrol, and urolithin A are some of the molecules being tested by researchers for anti-ageing effects,” said Prasad Kasturi, Assistant Professor, IIT-Mandi, Himachal Pradesh.
Ageing is frequently linked to disease. Cellular senescence, where damaged cells stop dividing, plays a role in ageing. These senescent cells can cause damage to the body by releasing harmful proteins.
Chemical pathway
“There are a lot of promising molecules that are entering clinical phases. Rapamycin is in small clinical trials, as also a number of senolytics,” says Pankaj Kapahi, Professor, The Buck Institute for Research on Aging, Novato, California. Senolytic drugs can eliminate senescent cells and this, in turn, may help prevent or treat age-related diseases in humans.
Kapahi’s research, which is likely to enter clinical trial this year, is titled ‘Glycation-lowering compounds inhibit ghrelin signalling to reduce food intake, lower insulin resistance, and extend lifespan’. According to the paper, glycolysis (breakdown of glucose by enzymes) can cause the build-up of a substance called methylglyoxal (MGO), which is linked to obesity and ageing issues.
Kasturi says it’s difficult to say more about the anti-ageing molecules under trial right now because “most of the time we don’t know the exact nature of the molecules that are under a clinical trial, but we have a wide variety of chemicals or molecules, chemical sensing molecules, natural molecules, phytochemicals, and a number of molecules that are known to modify lifespan in different model organisms”.
Kapahi says the ongoing efforts are mostly small-scale clinical trials in Phase I or II.
There are several common molecules that are potential candidates for studies related to anti-ageing. The diabetes drug metformin, for instance, is being investigated under a study titled ‘Metformin in ageing and ageing-related diseases: clinical applications and relevant mechanisms’. The findings suggest that metformin may slow the ageing process and provide protective benefits against the advancement of age-related diseases by influencing crucial events like protein maintenance, altered cell communication, changes in gene activity brought by environmental factors, and so on.
Rapamycin, used in cancer treatment, is considered another potential candidate for an anti-ageing drug. The research titled ‘Rapamycin treatment increases survival, autophagy biomarkers, and expression of the anti-ageing klotho protein in elderly mice’ suggests that rapamycin has a positive effect on ageing mice by boosting autophagy — the process that cleans up waste in cells, and cuts down harmful senescent cells.
In the study, two-year-old mice received rapamycin or a placebo. With rapamycin they survived the 12-week period, whereas 43 per cent of the control group died. Rapamycin caused slight weight loss and showed potential for reducing the inflammatory markers linked to ageing.
Health span
Can science then reverse ageing ?
“We need to do the experiments to better understand which molecules target which age-related pathologies. There is unlikely to be one silver bullet that will simply solve ageing. The basic science in the field will need to progress hand-in-hand to deliver better therapeutic targets to extend a healthy lifespan,” says Kapahi.
Parminder Singh, another researcher at the Buck Institute for Research on Ageing, says, “The main goal of ageing research is to extend healthy span, not lifespan per se. The idea is not to just add 10 extra years to your life; I think the idea is to, you know, improve your health span as well.”
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