Further Evidence for Cancer Treatments to Accelerate Aging

People who have undergone chemotherapy or radiotherapy suffer a reduced life expectancy and increased risk of suffering other age-related conditions even when the cancer is defeated. These cancer therapies produce large numbers of senescent cells, both as a result of their toxicity and because they force cancerous cells into senescence. It is quite likely that this is the primary mechanism by which successful cancer treatments nonetheless shorten later lifespan. This could be considered a true form of accelerated aging, as the accumulation of senescent cells is one of the root causes of aging. These cells secrete signals that meaningfully disrupt tissue structure and function even when present in relatively small numbers. The research noted here doesn't make the direct connection to cellular senescence, but the cell properties examined are strongly related to levels of senescence.

Treatments for breast cancer increase patients' risks for long-term and late toxicities, including persistent fatigue, pain, and cognitive dysfunction. Certain treatments, including radiation and some chemotherapeutic drugs, work by damaging the DNA of cancer cells, but they can also cause damage to DNA of normal cells, which can contribute to accelerated biological aging.

To examine whether indicators of biological aging are related to cognitive function in breast cancer survivors, researchers evaluated a group of 94 women who had been treated for breast cancer three to six years earlier. The indicators of biological aging included elevated levels of DNA damage, reduced telomerase enzymatic activity, and shorter telomere length in certain blood cells. (Telomerase is an enzyme that is important for maintaining the length of telomeres, repeat sequences of DNA at the ends of chromosomes that help maintain the health of cells and serve as a marker of cell age.)

The team found that women who had previously been treated for breast cancer who had both higher DNA damage and lower telomerase activity had lower executive function scores. In addition, lower telomerase activity was associated with worse attention and motor speed. Telomere length was not related to any of the neurocognitive domains.

Link: https://newsroom.wiley.com/press-release/cancer/cancer-treatments-may-affect-cognitive-function-accelerating-biological-aging


And I thought chemo drugs would disproportionately target senescent cells. I find this very interesting in that this past weekend (Fri-Mon) I did my 4 day water fast for November and was lamenting that I can't find a doctor to prescribe dasatinib to enhance the autophagy (Princeton Longevity took a pass on the off-label). So what chemo drugs were looked at in this study?

Posted by: Tom Schaefer at November 29th, 2018 8:35 AM

@Tom Schaefer
There was also radiation and breast cancer chemo. Dasatinib usually (if ever) is not used for breast cancer. Probably if the anti-cancer treatments are combined with senolytics the long-term damage can be reduced, and probably, even improve the chemo results...

However, we will need extensive human data to be sure. And that could take years after the senolytics become mainstream....

Posted by: cuberat at November 29th, 2018 9:34 AM

@Tom Schaefer

Some chemotherapy drugs are known to also target senescent cells, but that's dependent on the mechanism of action for the agents in question, and the specific of cells targeted by the drugs. Evasion of apoptosis and immune surveillance are hallmarks of both persistent senescent and cancerous cells, so chemotherapy drugs which target those hallmarks would be expected to have some senolytic activity. In contrast, drugs which target cellular replication mechanisms or telomere elongation would leave sensecent cells untouched while targeted cancer cells and stem cells alike.

It's that latter category of chemotherapy drugs that I would expect to accelerate aging.

Posted by: Dylan Mah at December 3rd, 2018 12:03 PM

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