Photo: De Visu – stock.adobe.com
How Scientists Are Working to Stop the Ageing Process
Forever young?
Many people dream of staying young for as long as possible. A formula for eternal youth would no doubt fly off the shelves. We’d like to introduce you to a few scientists who are working on delaying the ageing process.
Photo: De Visu – stock.adobe.com
Elizabeth H. Blackburn: Protective Caps for Genomes
Growing old in good health is easier if the protective caps at the end of each strand of DNA, the so-called telomeres, are intact. This hypothesis has been proven by molecular biologist Elizabeth H. Blackburn, who received the 2009 Nobel Prize in Physiology or Medicine along with Jack W. Szostak and Carol W. Greider. As early as 1985, Blackburn, who is originally from Australia, and Carol W. Greider discovered the enzyme telomerase, which is produced naturally in the body and protects the telomeres. Their findings created the basis for further research into topics such as ageing and cancer. [1]
Telomeres consist of specific, repeating DNA segments and proteins. They wrap themselves protectively around the ends of the human chromosomes – just like the plastic caps at the ends of shoelaces. As we age, cell division causes the telomeres in the body cells to shorten – except in the case of stem cells or the cells of the germ line, which divide continuously. The enzyme telomerase ensures that the telomeres are completely rebuilt during the cell division.
A healthy lifestyle “nurtures” the telomeres: the speed at which the length of the telomeres in the body cells decreases is determined by genes, but also by environmental influences such as nutrition. According to the therapeutic approach of Blackburn and her colleagues, people with healthy lifestyles – for example, those who avoid smoking or chronic stress – can “nurture” their telomeres and ensure they shorten more slowly. Blackburn and colleagues have shown in their research that short telomeres can lead to the formation of so-called senescent cells. Over time, these cells lose their normal function and cause a variety of age-related diseases.
Why do telomeres become shorter at all? The decrease in length is a protective mechanism against cancer, because cells with short telomeres are no longer able to divide. However, cancer cells activate the enzyme telomerase, which enables them to proliferate uncontrollably. The dual function of the enzyme telomerase, which can both promote cancer and halt ageing processes, has so far prevented its use in anti-ageing therapies. Nevertheless, the research for which Elizabeth H. Blackburn laid the foundations continues.
Cynthia Kenyon: Focus on Longevity Genes
Daf-2 is the name of one of the genes that may affect our lifespan: if it is modified or deactivated, the body goes into economy mode. Instead of growing, everything then revolves around the preservation of cells – and the lifespan is extended. In the nematode Caenorhabditis elegans, a roundworm species, a deactivation of the daf-2 gene can even double the lifespan. [2]
It was with this ground-breaking discovery that US molecular biologist Cynthia Kenyon caused a sensation in 1993. What is particularly interesting in this discovery is that the life-prolonging effect of a mutation in the daf-2 gene is not restricted to the nematode. Similar genes are also found in other species, such as the IRS-1 gene in mice and humans. Mice with deactivated IRS-1 genes live longer and remain healthier while ageing. [3] Daf-2 and IRS-1 are part of the so-called insulin/IGF-1 signalling pathway, which regulates the growth and survival of cells depending on the available nutrients. Drugs – rapamycin, for instance, an active substance that prolongs the lifespan of mice – can influence this signalling pathway. [4]
Cynthia Kenyon, a member of the US National Academy of Sciences and Vice President for Aging Research at Google’s Calico Research Labs, has become one of those pioneers of modern ageing research who no longer regard ageing as a passive, uncontrollable process. Since Kenyon’s findings, gerontologists have been assuming that the lifespan of humans could be extended by appropriate therapies, and that the onset of age-related diseases could be delayed.
Tony Wyss-Coray: Young Blood to Fight Alzheimer’s
What happens when you inject old mice with the blood plasma of young animals? Their memories regain the same power they had when young. In 2014, the Swiss scientist Tony Wyss-Coray, Professor of Neurology and Neurological Sciences at Stanford University in California, and his team corroborated this incredible hypothesis.
Only a few years later, the researchers proved that plasma in the human umbilical cord also contains certain proteins that keep us young – and act in old mice like a fountain of youth. [5] However, the answer to the question of whether these special blood substances could also help elderly people remains open. If it turns out to be “yes”, then novel drugs could in the future make diseases such as Alzheimer’s and Parkinson’s a thing of the past.
Wyss-Coray has founded a biopharmaceutical company with the aim of further advancing research into the deciphering of molecular processes in cells. The researchers at this company are currently conducting clinical studies with Alzheimer’s patients. [6] With his research, the medical scientist wants to enable people to grow old in good health – while delaying for as long as possible the onset of such diseases as dementia.
Nir Barzilai: Searching for the Anti-ageing Pill
Nir Barzilai, Professor of Medicine and Genetics at the Albert Einstein College of Medicine in New York and founding director of the Institute for Aging Research, is looking into ways of stopping the ageing process. His approach bases itself on the fact that people who’ve reached the age of 100 and beyond have certain gene variants that delay the ageing process and protect them against age-related diseases. With the discovery of a variant in the CETP gene, which is particularly common in people over 100, Barzilai’s team of researchers made the headlines in 2006. [7] They found out that the CETP gene plays an important role in cholesterol metabolism, and that elderly people with this gene variant are mentally fitter. However, attempts to directly influence the CETP gene with drugs had to be stopped due to unexpected side effects.
Nevertheless, Nir Barzilai is certain that new drugs could prolong our lives in the future – for instance, a pill being developed by Barzilai and his colleagues that contains the active ingredient metformin. Metformin is already approved worldwide as a drug for type 2 diabetes and is recognised as safe to use. Mice fed with metformin live longer. But can metformin also prolong the lives of humans and perhaps even prevent age-related diseases like dementia or cancer? A study initiated by Nir Barzilai, among others, is aiming to provide certainty. [8]
David A. Sinclair: Ageing is a Disease
David A. Sinclair is certain that, in the future, stem cell research and gene therapies will replace vaccinations and antibiotics. According to the Australian scientist, there is no upper limit to human life expectancy. The genetics professor at Harvard Medical School in Cambridge expects that scientists of the future will treat ageing as a disease and in this way postpone death.
However, what does such an anti-ageing therapy look like? It improves the repair function of ageing cells with the help of special anti-ageing drugs, says Sinclair, who is testing his methods on himself. Every day, the scientist takes various anti-ageing drugs that have been developed in biotechnology companies that he co-founded.
Among them is, for example, an active substance that stimulates the production of the molecule NAD (nicotinamide adenine dinucleotide) in the body: Sinclair’s research on mice has shown that the amount of NAD decreases with age and that administering NAD to old mice makes them healthier and prolongs life. Whether this also works in humans is still open [9] – to date no proof of a positive effect of NAD therapy has emerged. [10]
Judith Campisi: Rubbish Collection Service for Old Cells
Senolytics – drugs that remove from the body old cells that no longer function (so-called senescent cells) – are currently being talked up as a possible medicinal fountain of youth in the future. As we age, various factors – such as short telomeres or damage to the genetic material – prevent cells from dividing and cause them instead to give off harmful molecules that, for example, may degenerate into cancer cells. [11] If these senescent cells accumulate over the years and are not combated by the immune system, this can lead to diseases.
One of the pioneers in senolytics research is Judith Campisi, professor at Stony Brook University in New York and an entrepreneur. Her goal is to remove old cells from organisms and test how, and whether, the tissue can be rejuvenated – thereby preventing dementia, cancer or other diseases. Initial experiments on animals have already been successful and rejuvenation has been achieved. 12] The company founded by Campisi is currently conducting trials on humans. [13]
Sources and bibliography
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[2] https://www.nature.com/article...
[3] https://www.fasebj.org/doi/abs...
[4] https://www.nature.com/article...
[5] www.zeit.de" class="redactor-autoparser-object">https://www.nature.com/article...
[7] https://www.aerzteblatt.de/tre...
[8] https://www.pharmazeutische-ze...
[9] https://www.biorxiv.org/conten...
[10] https://sz-magazin.sueddeutsch...
[11] https://www.spektrum.de/lexiko...
[12] https://www.technologyreview.c...