Will Interventions that Improve Mitochondrial Function Also Increase Cancer Risk?

You may recall some speculative discussion regarding whether or not upregulation of NAD+ to improve mitochondrial function might increase cancer risk in old people. Much of the slowdown of aging, from reduced metabolism to reduced stem cell function, and certainly including loss of mitochondrial function, may influence lifespan by reducing the risk of cancer, while at the same time ensuring a slow decline into organ failure.

This topic remains speculative, but if NAD+ upregulation does in fact increase cancer risk, then it is possible that other approaches to restore mitochondrial function will also have this outcome. It could go either way: one important consideration is that a treatment that globally improves mitochondrial function will also tend to improve immune function, and the immune system acts to suppress cancer. Also consider that exercise does more to upregulate NAD+, and thereby improve mitochondrial function, than any of the assessed pharmacological approaches - and exercise certainly does not increase cancer risk.

Nicotinamide adenine dinucleotide (NAD) precursors and sirtuin-activating compounds (STACs) are becoming popular among longevity-minded individuals. The misguided conception that raising NAD or sirtuin activity can only have positive effects on human physiology should be considered erroneous and even deleterious. Hype exists around molecules that appear to extend life or slow down the aging process; however, little regard is given to the aberrant side effects or diseases that the upregulation of some molecules or overexpression of some proteins can cause, such as cancer.

Clearly NAD is used in all cells, including cancer cells, to produce energy. The findings of this review paper suggest that NAD supplementation should be discussed with a healthcare practitioner if you have a strong family history of cancer, have cancer, or have had cancer. Any given subject should first speak to their healthcare provider when considering NAD and possibly perform screening tests. However, NAD may fend off many other age-related diseases and prevent cancer from developing, so developing strategies to purge senescent cells from the body prior to NAD supplementation should also be considered.

The pursuit to blindly raise sirtuin activity in the quest for longevity may also produce counterproductive results and may be misguided. However, cancer cells like normal cells require the same cellular machinery to function, and this review does not find that NAD nor sirtuins cause cancer but may simply assist fuelling cancer where present. Where it is shown that sirtuin or NAD inhibition shows beneficial effects against cancer progression, it does not infer those elevated levels of sirtuins or NAD assist in cancer progression but are simply part of the cancer progression. Raising sirtuin or NAD activity may increase disease penetrance, and further research is required to understand the complex mechanisms at play.

Link: https://doi.org/10.1002/agm2.12184


NAD+ can speed the progress of an existing cancer but will it cause more cancer if the mitochondrial damage is reduced in the first place?

Posted by: Cuberat at January 7th, 2022 9:53 AM

It is interesting to see the exact same arguments and counter arguments used around telomerase activators being used again here.

Posted by: Mark at January 10th, 2022 6:18 AM
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