Tue. Aug 20th, 2019

The slow progress towards treatments for human aging | Science



Eighty years ago, in 1939, a team from Cornell University (USA) led by Clive McCay managed to prolong life of rats reducing the calories in their diet. In addition, he noted that those animals also suffered less aging-related diseases. These findings, which have been replicated in different species of animals during subsequent decades, are the first indication that the aging process is not something immutable. Cornell rats came to live 33% more thanks to a restricted diet that maintained the necessary nutrients and served as an example for scientists who later tried to find out if prolonging our life is a crazy dream.

Years later, studies with worms Caenorhabditis elegans showed that the modification of a single gene, age-1, could increase the life span of mutants by 40 to 60%, and work with flies or rodents has helped identify molecules or genetic manipulations that can do Vary the longevity of these animals. But transferring that progress to our species is another story.

Aging is the main risk of suffering many diseases, but the causality has not been proven

Almost a century after the experiments with rats of McCay and his own, the US National Institute on Aging warns that, although some studies indicate that caloric restriction may have health benefits in humans, there is no evidence to show its link to longevity. Some measures to prolong our life seem promising, but nothing is conclusive. However, a recent review of studies on the increase of longevity and healthy years of life published in Nature suggests that there are indications that the first successes may be close.

At work, signed by Eric Verdin and other leaders of the Buck Institute for Aging Research in Novato, California, recalls efforts to understand what aging is and why it affects our health so much. Despite the advances, the mystery of what happens to us over the years continues to be present in the difficulties in identifying aging as the cause of diseases that worsen with age. "The use of the word ‘cause’ remains controversial because, although aging is the greatest risk factor for a multitude of age-related diseases, causation has not been proven, "the Buck scientists write.

In a published article in the magazine JAMA in 2018, Tamara Tchkonia and James Kirkland, from the Mayo Clinic in Minnesota (USA), broadly identified four aging-related processes: chronic inflammation, cell dysfunction, changes in stem cells that lose their ability to regenerate tissues and the accumulation of aging cells in tissues that is related to disease.

According to Verdin, in the first years of studies on aging, the researchers made two discoveries that can be useful in combating it. On the one hand, the number of genes that can be manipulated to extend the life of an organism are many more than previously thought, "something that suggests that the plasticity of the aging process is much higher than expected." Second, the genes that control aging are well conserved in organisms as different as yeasts, worms, fruit flies and humans. This makes, in principle, the strategies that are used in model organisms such as C. elegans or Drosophila and that they have succeeded in prolonging their lives, they can also have it in the long term in humans.

Among the substances that may be useful for prolonging life at some point, Verdin and his colleagues point out some whose potential has been known for a long time, but which are beginning to approach clinical trials with humans. Rapamycin, which has managed to prolong the life of laboratory mice by 38% and can improve the functioning of stem cells in older people, is one of the drugs identified by the ITP program of the National Institute for the Aging of the USA with possibilities to extend the life in animal models. A clinical trial has already tested its effects on cardiac function, cognition, cancer and life expectancy in domestic dogs as an animal model prior to its application in humans.

Metformin is another drug that has aroused interest for years. Prescribed against diabetes, it has been observed that it acts on various mechanisms related to aging. In diabetic patients, it improves cardiovascular health and delays death and in worms and mice it has achieved vital extensions of 57 and 6% respectively. However, conducting studies to see how it works with healthy humans is not easy. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein Medical School in New York, has designed a study, the TAME, to treat aging with metformin, but there are still doubts about whether it will achieve adequate financing to boost it with chances of success.

The authors of the review of Nature remember in any case that analyzes of anti-aging treatments should measure their effects on factors related to the passage of age and not only on specific ailments. Fragility, dementia or the combination of old age diseases could be a measure to add to other features such as grip strength, walking speed or resistance to infection. In this sense, there are still biomarkers to develop, such as some epigenetic brands, that serve to measure aging and treatments to stop it, in an objective way. In addition, scientists know that, although a treatment was developed with some efficacy for one group of people, it could be useless or even harmful to another.

For those who see little concreteness in the summary of advances against the aging of Verdin and his companions, these scientists offer advice and a doubt. In the absence of treatments to slow down the effect of time in humans, the authors point to exercise as the only proven effective intervention against diseases associated with old age. "Its benefits can be seen even with modest practice," they say. Regarding the diet, although they claim that it is one of the main influences on health and aging, they consider it “very difficult to carry out rigorous long-term studies to compare the effects of different diets on life expectancy and the time that you live with health ”. "Without direct comparisons of this type, no specific diet can claim to be superior to another," they conclude.

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