An infrequently discussed topic in aging circles is the point that we should probably expect any therapy that improves tissue maintenance and regeneration in old people to also increase cancer risk. There isn’t much in the way of evidence to support that position, but it seems worthy of consideration. Cancer is a numbers game, and the greater the activity undertaken by stem cells and progenitor cells, the greater the likelihood of cancerous mutations. The only exceptions are interventions that act to improve the function of the immune system in addition to any other benefits that they produce; such treatments could lead to a net reduction in cancer risk, due to improved immunosurveillance of potentially cancerous cells. A plausible example of this type of treatment is telomerase gene therapy, though it remains to be demonstrated that improved immune function is the mechanism by which cancer risk is reduced in animal studies.
With this in mind, researchers here show that too much klotho can increase cancer risk in cancer survivors. Cancer survivors exhibit a greater risk of later cancer mortality than other age-matched individuals. This is in part due to the risk of recurrence of the treated cancer, but also because chemotherapy and radiotherapy stress cell populations to produce an increased burden of cellular senescence in these patients. Greater levels of klotho correlate with greater longevity in the population at large, but to the degree that greater longevity goes hand in hand with increased cell activity, regenerative capacity, and tissue maintenance, then it will also increase the risk of cancer. It should be easier to quantify that risk in the epidemiological data for cancer survivors than in the general population, and hence this study.
Circulating Klotho and mortality patterns among US cancer survivors: A cohort study
Klotho, a longevity hormone, exerts diverse anticancer activities. However, evidence regarding the association between serum Klotho and mortalities among cancer survivors is lacking. We examined the association between serum Klotho and the risks of all-cause and cancer mortalities among 1602 cancer adults from the National Health and Nutrition Examination Survey (NHANES) (2007-2016) using multivariate Cox proportional hazard models. The nonlinear relationship was determined using the likelihood ratios test, and the inflection points and 2-piecewise Cox proportional hazards regression models were computed.
After a median follow-up period of 84.0 months, U-shaped associations between circulating Klotho and all-cause and cancer mortality were observed, with identified inflection points (pg/mL) of 765.5 for all-cause and 767.6 for cancer mortality. Klotho below these thresholds was inversely associated with all-cause mortality (Hazard ratio, HR = 0.72) and cancer mortality (HR = 0.61; Klotho above the threshold showed a trend of positive associated with cancer mortality (HR = 1.22). Effect modification of age was apparent; Klotho was associated positively with cancer mortality risk among participants aged under 60 (HR = 1.50). The U-shaped associations between serum Klotho and all-cause and cancer mortality indicate that maintaining an ideal Klotho level in cancer patients could reduce mortality risks.
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