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A High Level View of Senescent Cell Clearance

This is a better than average popular science article on turning back the progression of aging by removing senescent cells from aged tissues; certainly the bar for article quality set by the mainstream press isn't high, but it is always pleasant to see more authors clearing it. One point worth noting in response to this piece is that we really have little idea as to how the life extension observed in mice lacking senescent cells will scale in humans. Near all methods of extending life in mice to date have been based on modestly slowing aging, changing the operation of metabolism to reduce the rate at which molecular damage accrues. Short-lived species like mice have a much greater response to this sort of thing than do humans, demonstrated when we compare the effects of calorie restriction and growth hormone receptor loss of function mutations. In mice these can extend life by as much as half again, but if that was the case in humans, we'd have certainly noticed by now. Clearing senescent cells is a completely different form of therapy, however, a type of damage repair carried out intermittently rather than an ongoing slowing of damage. I know of no such approach that has been tried in both mice and humans, and thus there is no basis for comparison.

Imagine a world where you could take just a single pill for the treatment or prevention of several age-related diseases. Although still in the realms of science fiction, accumulating scientific data now suggests that despite their biological differences a variety of these diseases share a common cause: senescent cells. This has led scientists to find drugs that can destroy these cells. When cells become damaged, they either self-destruct (apoptosis) or they lose their ability to grow and remain stuck within the body. These are the non-growing senescent cells that no longer carry out their tasks properly. They spew out chemicals that cause damage to cells nearby, sometimes turning them into "zombies" - hence why they are sometimes referred to as "zombie cells". Eventually, the damage builds up so much that the function of bodily organs and tissues, such as skin and muscle, becomes impaired. At this point, we identify the changes as disease.

In 2011 and in 2016, researchers showed, through the use of genetically engineered (transgenic) mice, that the removal of senescent cells reduced cancer formation, delayed ageing and protected the mice against age-related diseases. The mice also lived 25% longer, on average. A similar result in humans would mean an increase in life expectancy from 80 years to 100 years. It was proof-of-principle studies like these that laid the groundwork and inspired other researchers to build on these findings. It is not known how many senescent cells need to be present to cause damage to the body, but the harmful effects of the chemicals they release can spread quickly. A few zombie cells may have a huge impact. Drugs for specifically killing senescent cells in order to extinguish their destructive force have recently been revealed and tested on mice. The collective term for these drugs is "senolytics".

In 2016, two research groups independently published findings on the discovery of two new senolytic drugs which target proteins responsible for protecting senescent cells from cell death. Research showed that the drug ABT-263 (Navitoclax) could selectively kill senescent cells in mice, making aged tissues young again. And scientists have also used the drug ABT-737 to kill senescent cells in the lungs and skin of mice. There has also been a lot of interest in the role of senescent cells in pulmonary diseases caused by damage to the lungs. In late 2016, scientists showed that the removal of senescent cells using genetically engineered mice greatly restored lung function in old mice. In light of these accumulating and highly promising findings, a number of start-up biotechnology companies have been created to exploit the health benefits of targeting senescent cells. Probably the most well funded is UNITY Biotechnology in the US which raised US$116M for research and development.

Link: https://theconversation.com/killing-zombie-cells-to-improve-health-in-old-age-74557

Comments

Is the S.C.C. lifespan extending mechanism independent from IGF1 reduction? If yes, SCC should be tested on mice with Laron syndrome. Theese species thave already a very low IGF1 level and the don't have any lifespan boosting benefits from calorie restriction or fasting.

Mice with Laron syndrome are the species with the longest lifespan and all present day (gen1) geroprotectors don't work on them (ARB, propranolol, metformin, fasting,...)
Hormesis induction geroprotectors are inefficient.

Conclusion: mice with Laron syndrome are good candidates to test all the next gen geroprotectors (garbage cleaners, gen2).

Posted by: Denis Varvanets at March 20th, 2017 7:45 AM

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