Why Old Age May Soon Look Very Different: Senolytics, A New Class Of Drugs, Slows Aging Process

aging
Senolytics, a new class of drugs, might dramatically slow the aging process and so change the face of old age. Photo courtesy of Shutterstock.

Senescence, the loss of a cell's power to divide and grow, is a fundamental aging process believed to contribute to chronic diseases and age-related dysfunction. So what if you could stop this process? A recently published study offers proof from animal experiments that senolytics — a new class of drugs that selectively kill senescent cells — might dramatically slow the aging process and extend health during the lifespan.

“It may eventually become feasible to delay, prevent, alleviate, or even reverse multiple chronic diseases and disabilities as a group, instead of just one at a time,” Dr. James Kirkland, senior author of the new study, stated in a press release.

Many chronic diseases share a single common risk factor: aging. Yet, it is well-known that this everyday aging process is accelerated by accumulating senescent cells. In experiments where scientists kill senescent cells in mice, the small rodents' time where they live free of disease (healthspan) is lengthened and enhanced. Isn’t it natural to wonder if the same might be true in humans?

Before they could test this what if, the team of scientists working at Mayo Clinic, the Scripps Research Institute, and other institutions first investigated how to identify and target senescent cells without damaging all the other healthy cells. In particular, they concentrated on the reasons why senescent cells resist death caused by stress and damage. After all, these cells are damaged and malfunctioning, it seems only natural they would be quick to die first.

What the team discovered was senescent cells have a greater expression of pro-survival mechanisms and, just like cancer cells, these up-regulated mechanisms help the cells resist programmed death (apoptosis).

Having made this discovery, the research team worked backward and looked at all the available compounds to see if any interfered with the up-regulation of pro-survival mechanisms in cells. They found a number of likely suspects, yet after tests and analysis they narrowed the field down to two compounds: the cancer drug dasatinib (Sprycel) and quercetin, a natural supplement that acts as an antihistamine and anti-inflammatory.

In cell cultures, these compounds selectively killed off senescent cells. Each had different strong points, so the team tested a cocktail of the two and this proved to be most effective overall. Next, the researchers conducted tests to see how these drugs might affect the health of aging mice.

Remarkably, dasatinib and quercetin reduced osteoporosis and frailty, improved cardiovascular function as well as endurance, and extended the healthspan of the mice. Within five days of a single dose of the drugs, cardiovascular function was improved in the oldest mice. A single dose of the drug cocktail led to improved exercise capacity — as measured by the mice running on miniature treadmills with the positive effects lasting for seven months or more. When the drugs were given periodically, the mice demonstrated delayed age-related symptoms, spine degeneration, and osteoporosis.

Clearly, more testing would be necessary before humans get the opportunity to test run these drugs for their anti-aging benefits, and it's clear both compounds have side effects. However, this does not deter the ever-hopeful scientists.

“An advantage of single doses or periodic short treatments is that many of these side effects would likely be less common than during continuous administration for long periods,” they write in their published research, “but this needs to be studied.”  

Study away, study away… the aging world awaits you.

Source: Zhu Y, Tchkonia T, Pirtskhalava T, et al. Achilles’ Heel of Senescent Cells: From Transcriptome to Senolytic Drugs. Aging Cell. 2015.

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