SenMayo Based Aging Signature (Sen-Age) in cancer survivors: The Health and Retirement Study (HRS)

TL;DR

This study uses a gene-based aging signature to predict mortality in cancer survivors, showing that higher aging scores correlate with increased risk of death.

Contribution

The novel Sen-Age signature is developed and validated as a biomarker of aging and mortality specifically in cancer survivors.

Findings

Sen-Age is strongly correlated with chronological age in cancer survivors (correlation of 0.46).

Higher Sen-Age scores are associated with increased 4-year mortality risk in cancer survivors (HR: 1.47).

Cancer survivors have significantly higher Sen-Age scores than non-cancer controls.

Abstract

The SenMayo gene set identifies senescent cells, one of the hallmarks of aging, especially among those with cancer. In the HRS cohort, we constructed a SenMayo based aging signature (Sen-Age) among those without cancer (controls) and examined its association with 4-year mortality in cancer survivors. In the 2016 wave, HRS measured 125 SenMayo genes in blood samples. We applied Lasso regression to participants without cancer in 2016 (N = 3076) and trained SenMayo genes against chronological age; this resulted in a subset of 97 genes with which we created Sen-Age. This Sen-Age signature demonstrated a correlation of 0.46 with chronological age in 609 cancer survivors. We then examined the associations of Sen-Age with 4-year mortality (N = 112) in cancer survivors using Cox Proportional Hazards regression model after adjusting for age, sex, and race. Sen-Age was associated with increased risk of mortality in cancer survivors (HR: 1.47 [1.17–1.85] per 1 year, p = 0.0008). This association remained robust (HR: 1.31 [1.04–1.66], p = 0.02) upon additional adjustment for education level, smoking status, BMI, inflammation and comorbidities. Moreover, cancer survivors have higher Sen-Age score (adj mean: -0.44 ) than non-cancer controls (adj mean: -0.83). Overall, our findings highlight the potential of the Sen-Age signature as a biomarker of aging and mortality in cancer survivors.