Protein Signatures of Aging Suggest a Slower Pace of Aging in Centenarians

Researchers here build a signature of aging based on age-related changes in the proteins found in blood samples, and then show that centenarians appear to undergo these changes more slowly than people who die at younger ages. One would expect to see that a population of exceptionally old people achieved a long life by aging more slowly than their peers: aging is, after all, defined as an increase in the risk of mortality over time due to intrinsic causes. The question is how one can measure differences in the pace of aging more efficiently than by waiting for years to observe outcomes in mortality.

The development of measurements of biological age that can be carried out fairly quickly given a blood or tissue sample, such as epigenetic clocks, is an important topic in aging research. A simple, reliable biomarker of aging could greatly accelerate the assessment of potential rejuvenation therapies, allowing researchers to discard less useful paths and focus on those with better outcomes.

Using samples from the New England Centenarian Study (NECS), we sought to characterize the serum proteome of 77 centenarians, 82 centenarians' offspring, and 65 age-matched controls of the offspring (mean ages: 105, 80, and 79 years). We identified 1312 proteins that significantly differ between centenarians and their offspring and controls, and two different protein signatures that predict longer survival in centenarians and in younger people. By comparing the centenarian signature with two independent proteomic studies of aging, we replicated the association of 484 proteins of aging and we identified two serum protein signatures that are specific of extreme old age.

The data suggest that centenarians acquire similar aging signatures as seen in younger cohorts that have short survival periods, suggesting that they do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence-associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this finding, we provide a new list of serum proteins that can be used to measure cellular senescence.

Protein co-expression network analysis suggests that a small number of biological drivers may regulate aging and extreme longevity, and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging and provides specific circulating biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.



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