Protein signatures of centenarians and their offspring suggest centenarians age slower than other humans

Abstract

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 (FDR < 1%), and two different protein signatures that predict longer survival in centenarians and in younger people. By comparing the centenarian signature with 2 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.

The association between nutritional status and functional limitations among centenarians: a cross-sectional study

“…Current research mainly focuses on European populations and the sick older [ 13 – 16 ], with a lack of studies on Asian populations and community older. Centenarians, as the “template population” of population aging, have reference value for the extension of their life span and health to the general older population [ 17 ]. The longevity of centenarians in China’s Hainan Province is closer to natural longevity than that of those in areas with higher level of economic and medical.…”

Peroxisomal Stress Response and Inter-Organelle Communication in Cellular Homeostasis and Aging

“…Conversely, the overexpression of Pex5 has been shown to restore peroxisomal import function and preserve cardiac health in aged oenocytes [ 14 ]. Importantly, Sebastiani et al [ 169 ] studied the proteomic signatures of centenarians and identified that proteins encoding components of peroxisomes were significantly downregulated in centenarians’ serum compared with younger individuals. In addition, the bile acid metabolism pathway and cholesterol homeostasis pathway were also downregulated in centenarians.…”

Ranking Biomarkers of Aging by Citation Profiling and Effort Scoring

“…In response to mitochondrial dysfunction, growth differentiation factor 15 (GDF15) may be generated, protecting tissues against inflammation by suppressing T-cell activation and mediating release of cytokines (Moon et al, 2020). On this basis, GDF15 was suggested as a potential aging biomarker (Justice et al, 2018;Tanaka et al, 2018;Basisty et al, 2020;Sebastiani et al, 2021). TGF-β and GDF11 (from the same protein superfamily) are also regarded as proteins playing a role in aging-associated cellular senescence, frailty, stem cell aging and fibrosis as well as surgical risk in older adults (Schafer et al, 2016;Khan et al, 2017;Niedernhofer et al, 2017;Bai, 2018;Dodig et al, 2019;Tominaga and Suzuki, 2019).…”