The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 10 No. 1 • March 2007

Combinations of Biomarkers Predictive of Later-Life Mortality

An interesting recent study1 examined 13 biomarkers as predictors of mortality over a 12-year period in a sample of 530 men and 659 women 70–79 years old. These individuals were part of a cohort of older adults from the MacArthur Study of Successful Aging, a prospective epidemiological investigation of factors associated with healthy aging.

The biomarkers examined different systems, including: cardiovascular [systolic blood pressure (SBP) and diastolic blood pressure (DBP)]; neuroendocrine [epinephrine (EPI), norepinephrine (NE), cortisol, and dehydroepiandrosterone (DHEA)]; metabolic [HDL-cholesterol, total/HDL-cholesterol, glycosylated hemoglobin (HbA1c, a measure of long-term glucose levels)]; and immune [IL-6, fibrinogen, C-reactive protein (CRP), and albumin]. Note: low levels of DHEA, HDL-cholesterol, and albumin are high-risk (HR), whereas low levels of the other markers are generally favorable.

Their general strategy was to examine different combinations of these markers to develop differential predictions of mortality for male and female subjects. The high-risk (HR) combinations in men were those in which the subgroups having that combination had greater than or equal to 70% dead within the 12 years. For the men, 11 of the 13 biomarkers enter into HR pathways: cortisol, CRP, IL-6, fibrinogen, NE, EPI, HbA1c, HDL-cholesterol, DHEA, and SBP and DBP. For the women, only 6 of the 13 biomarkers enter into HR pathways (greater than or equal to 60% dead): SBP, DBP, HbA1c, CRP, IL-6, and DHEA.

For 106 men in HR pathways, there was a cluster of five biomarkers that occurred together at elevated levels: CRP, IL-6, fibrinogen, NE, and EPI. In this subgroup of men, 71.7% had all five of these biomarkers at elevated risk levels, 97.2% had four or more of the five biomarkers, and 100% had three or more of the five biomarkers at elevated risk levels.

For 29 women in HR pathways, there was a cluster of four biomarkers occurring frequently: SBP, CRP, IL-6, and HbA1c.

Overall, significant gender differences were found. “Elevated SBP occurs in 100% of the HR female pathways and in only 17% of the HR male pathways. Fibrinogen, NE, and EPI, individually and in combination, dominate male pathways but do not even occur in female pathways. CRP and IL-6 occurred frequently in both male and female HR pathways.”

As the authors explain, limitations of the study included: (1) biomarker information was obtained at a single measurement point at the beginning of the study; (2) these adults were recruited for participation on the basis of high levels of cognitive and physical functioning, hence results may not be the same for lower-functioning adults; and (3) the analysis did not include other risk factors or health-promoting behaviors.


  1. Gruenewald et al. Combinations of biomarkers predictive of later life mortality. Proc Natl Acad Sci USA 103(38):14158-63 (2006).

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