Plasma Proteome Profiling of Centenarian Across Switzerland Reveals Key Youth-Associated Proteins.

Centenarians exhibited 583 differentially expressed proteins (DEPs) compared to both hospitalized geriatric patients and younger healthy participants.

• Geriatric patients were aged 80–90 years and were hospitalized; younger healthy participants were aged 30–60 years.
• The centenarian plasma samples were drawn from the SWISS100 cohort across Switzerland.
• Proteomics was used to characterize immune and cardiometabolic profiles of centenarian plasma.

Twenty-three proteins identified in centenarians were replicated against a standard set of aging proteins developed by the TAME (Targeting Aging with Metformin) consortium.

• The TAME consortium aging proteins served as an independent reference set for replication.
• 23 of the centenarian DEPs showed association with these established aging proteins.
• This replication step validated a subset of the centenarian proteomic signature against an external standard.

Comparison with an independent centenarian proteomics study identified 135 DEPs shared between both studies with identical aging directions.

• The 135 overlapping proteins showed concordant directionality of expression changes in both studies.
• This overlap established a 'robust set of aging proteins in centenarians' across independent datasets.
• The cross-study replication strengthens confidence in these proteins as centenarian-associated biomarkers.

Fractional polynomial regression analyses identified a subgroup of 37 proteins with a 'younger signature' in centenarians.

• Fractional polynomial regressions were applied to uncover proteins with both linear and non-linear age-associated profiles.
• The 37 proteins were characterized as having expression levels in centenarians more similar to younger individuals than to the older geriatric comparison group.
• These proteins were identified from the broader set of DEPs as representing a 'youth-associated' proteomic pattern.

Protein-protein interaction and pathway enrichment analyses of the 37 youth-associated proteins implicated five major biological processes.

• The five pathways identified were: programmed cell death, metabolic enzyme pathways, regulation of extracellular matrix stability, immune and inflammatory responses, and neurotrophic signaling pathways.
• These pathways were identified through protein-protein interaction network analysis combined with pathway enrichment analyses.
• The authors suggest these pathways 'may present promising targets to understand processes associated with longevity and healthy aging.'