Slowing Aging With... Cancer Drugs?

Aging is natural and happens to everyone, eventually. But that doesn't stop scientists from trying to find ways to either slow the process or mitigate the symptoms related to aging. New research looks at how a class of cancer drugs may play a role in allowing the body to rid itself of older cells, thereby easing the physical effects of growing older.

Scientists have long wondered if it would be possible to find interventions that would allow for a well-rounded "aging treatment" that would not only prolong lifespan, but would also allow for better health and enjoyment at older ages.

Age-Related Physical Symptoms & Disease

As we age, physical dysfunction and a hampered ability to respond to stresses become amplified, with just under half of people over the age of 85 being classified as "frail." This is associated with many different issues, like decreases in mobility and increases in age-related disease, and often translates into a loss of independence, nursing home and hospital admissions, and mortality.

The cellular development of age-related physical decline is not yet fully known, which means that we don't have any current treatments that would target the root of the problem and help to improve physical function in old age. Researchers wanted to look at a way to address this need by reducing the senescent cell burden.

A Look At Cellular Aging (Senescence)

Cellular senescence, or cellular aging, involves changes in gene expression and can be induced by things like DNA damage, the shortening of telomeres, and inflammation, among others. One of the hallmarks of senescent cells is that they secrete proinflammatory cytokines, chemokines, proteases, and other factors. This is known as "senescence-associated secretory phenotype" (or SASP), and is a contributing factor in local and systemic age-related dysfunction (as well as in a number of diseases). The research team wanted to see whether senescent cells play a part in age-related physical dysfunction and if they could improve both length of life and quality of health by targeting them in a therapeutic way.

In the course of their research, the scientists found that the proportion of aging cells in mice is related to aging-related symptoms like frailty, lower endurance, and slower walking speeds.

Senescent Cells in a Mouse Model

By taking differing amounts of senescent cells from older mice (tagged for tracking purposes) and transplanting them into younger mice, the team was able to analyze the function of these young mice with older cells compared to young mice who received placebo cells. The scientists noticed that the mice who received the senescent cells started to walk more slowly, and they exhibited impaired grip strength and endurance.

When looking at where in the body the senescent cells had taken hold, the researchers found that the cells had spread to tissues throughout the body, well beyond where the original transplant was located. They also observed that age-related physical issues seemed to appear when the senescent cells accounted for one in 7,000-15,000 cells overall. It also was observed that the senescent cells passed their accelerated aging to healthy cells through SASP.

Treating Senescent Cells with Cancer Drugs

Once the researchers understood that senescent cells played a role in age-related physical decline, they wanted to test whether it would be possible to eliminate these cells using a cancer drug (dasatinib) in combination with quercetin (a flavonoid known to have anti-inflammatory and antioxidant properties). Both of these strip senescent cells of their cellular protection against SASP.

Aging cells are similar to cancer cells (although they don't divide) in that they are protected from immune system attacks. The cancer drugs "expose" these cells, making them vulnerable. The scientists found that by targeting senescent cells in this way, they were able to trigger the process of apoptosis (cellular death) by disabling the defenses of these cells for only an hour or two.

In the group of mice who received the senescent cells along with the drug combination, lifespan was increased by 36% compared to the group who received the senescent cells alone. Not only did they observe an increase in lifespan, but the mice who also received the drug combination were also observed to be healthier and less frail until time of death.

Where the Research is Headed

This is only one study, and done in a mouse model, so the researchers caution against considering this a fountain of youth just yet. More studies are needed to better understand these results before clinical trials can be considered.

Still, many senolytics (drugs targeting senescent cells) have been described in an emerging range of studies, and early human trials are on the horizon. Scientists hope that this will be the start of discovering whether or not these types of drugs can help to rid the body of aging cells, whether they are safe, and if they can actually improve physical function in people.

Further Reading & References:

TIME: How Scientists Are Testing Cancer Drugs to Slow Down Aging. 09 July 2018. http://time.com/5333752/aging-drugs

Senolytics improve physical function and increase lifespan in old age. Nature Medicine, Volume 24, pages 1246-1256 (2018). https://doi.org/10.1038/s41591-018-0092-9

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