Researchers have for some years been casting a very broad net in terms of trying to understand how centenarians, people who survive to age 100 and beyond, are different from those who die at earlier ages. There is plenty of evidence for a fairly distinct biochemistry, such as better immune function and lesser degrees of chronic inflammation. Centenarians are still greatly impacted by the processes of aging, are frail, and exhibit a high mortality rate, so it is not a state to emulate, but it is hoped that this sort of research could help to better understand which aspects of aging are the most important in terms of driving declining function and rising mortality, and thus merit greater attention from the research community.
Centenarians exhibit remarkable longevity and compression of morbidity making them an ideal population for uncovering proteins associated with successful aging. Using proteomics, we characterized the immune and cardiometabolic profiles of centenarians’ plasma from the SWISS100 cohort. We identified 583 differentially expressed proteins (DEPs) by centenarians when compared with hospitalized geriatric patients (age 80-90 years) and younger healthy participants (age 30-60 years). We replicated the association of 23 proteins with a standard set of aging proteins (APs) developed by the Targeting Aging with Metformin (TAME) consortium.
By comparing the centenarian signature to an independent centenarian proteomics study, we identified 135 DEPs in both studies with identical aging directions, establishing a robust set of APs in centenarians. Applying fractional polynomial regressions, we uncovered proteins with linear and non-linear profiles associated with age and identified a subgroup of 37 proteins with a younger signature in centenarians. Protein-protein interaction and pathway enrichment analyses of 37 proteins point to programmed cell death, metabolic enzyme pathways, regulation of extracellular matrix stability, immune and inflammatory responses, and neurotrophic signaling pathways. This novel approach to aging research has uncovered new proteins and pathways, which may present promising targets to understand processes associated with longevity and healthy aging.
