Protein Signatures of Centenarians and Their Offspring Suggest Centenarians Age Slower than Other Humans

We used a high-throughput Somascan platform to quantify 4116 proteins in the serum of 224centenarians, offspring, and controls (mean ages: 105, 80, 79 years) from the New England Centenarian Study, and to characterize the serum proteome of aging and longevity. We identified 1312 proteins that significantly differ between centenarians and their offspring and controls (FDR<1%), and replicated the association of 484 of these using 2 independent proteomic studies of aging. By comparing the patterns of proteins associated with aging to protein profiles of centenarians, we also identified serum-protein signatures of extreme old age and of immune senescence. We then searched for protein signatures that distinguish between short and long survival within various age groups and we identified two differentprotein signatures that predict longer survival in older people and in centenarians. The data suggest that centenarians acquire similar aging patterns as seen in younger cohorts that have short survival periods, suggesting that centenarians 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 findingwe provide a new list of serum proteins that can be used to measure cellular senescence. Consistently with this findings, protein co-expression network analysis showed that the serum proteome of offspring and controls clusters in a small number of modules of correlated proteins, some of which are conserved in centenarians’ serum while others break down in smaller modules thus suggesting that a small number of biological drivers may regulate aging 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 biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.