Odgovor Pe maj 10, 2019 06:24

Extending Healthspan May Be Coming Soon

Excerpts based on Judith Campisi interviews: In the early 1990s research on the basic mechanisms of cancer revealed cells enter a senescence phase that prevents them from becoming cancerous, more than 25 years later this insight has led to a new kind of drug that may slow or even modestly reverse human aging.

Senescent cells undergo a transition into a zombie state where they are still active but no longer divide; research has shown this was a strategy to derail incipient cancers characterized by runaway cell division and growth. However these senescent cells accumulate with age and secrete an array of molecules that promote tissue degradation associated with aging.

In recent years such insight has led to the discovery of a new class of senolytic drugs which can eliminate senescent cells, and in animal studies have restored more youthful characteristics. Unity Biotechnology has launched human trials of its first senolytic drug in July 2018.

Thanks to advances tools are available now that were not available a few decades ago making to possible to conduct experiments that were once thought to be impossible. Paired with recognition of senescent cells as being one of the drivers of aging, we may now be able to see if these drugs will work in people.

Senescence is part of an evolutionary balancing act, selected for the worthy purpose of preventing cancer, because if cells are not able to divide they can’t form a tumour. This also optimizes tissue repair, but the downside is if these cells persist, as in aging, they become deleterious. From an evolutionary stand-point, evolution does not care what happens to you after you have passed the age of procreation, so after you hit 50 there are no mechanisms to effectively eliminate these cells in old age, and they tend to accumulate. Thus the idea of finding a way to eliminate these cells and seeing if tissue can be restored to a more youthful state has become rather popular.

Aging can be seen as a driver for multiple age related pathologies, geriatricians today take a more holistic approach and interventions are also more holistic, this idea has revolutionized the way we think about medicine. 80% of patients in the hospital for acute medical attention are aged 65+, senolytics may be one of the tools in the arsenal of weapons that geriatricians will have to use in treating aging holistically as opposed to a single disease at a time.

We don’t know enough to say whether it will be possible to extend human life, but average lifespan has already been done, maximum on the other hand is something different and we really don’t know. Looking at C. elegans the record for extending lifespan is 10 fold, moving up the evolutionary scale to look at the Drosophila fruit fly it’s about 2 fold, if you look at mice most high profile studies have extended it’s lifespan 20-30%. Looking at the differences between humans and mice, even though we are about 97% genetically identical, there is a 30 fold difference in lifespan. It is only logical to think in order for evolution to evolve a 30 fold difference in lifespan with so few clear genetic differences evolution had to tweak thousands of genes, at present it is unlikely that we will find a single drug capable of doing just as evolution did; people are welcome to think and believe what they like, but based on data that belief alone doesn’t make it true.

Medical interventions will no doubt extend healthspan, which in turn could extend lifespan a little. To some that’s a scary thought, most don’t want to live longer if that means having to live without mobility, cognitive function, and independence. But most wouldn’t mind living a bit longer if it could be done without losing those important details. Science appears to be on the cusp of understanding enough about the aging process to intervene.

That being said we all will still die. In the mouse models with eliminated senescent cells there was an increase in median lifespan but no increase in maximum lifespan. So the healthspan was increased, meaning they died healthier, and that is what the goal of anti-aging medicine is all about. This kind of intervention is broadly applicable and very desirable, who wants to live longer and feel that way, but living a little longer while feeling healthy is different. Conflict in the field comes into play with those who think we will live to be 200+ which at this point in time is not realistic, the science isn’t there.
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