# Plasma Proteome Profiling of Centenarian Across Switzerland Reveals Key Youth‐Associated Proteins

## TL;DR

This study finds proteins linked to healthy aging in centenarians, highlighting immune and metabolic pathways that could help promote longevity.

## Contribution

The study identifies a robust set of aging-associated proteins and a subgroup with a 'younger' profile in centenarians, validated across multiple datasets.

## Key findings

- 583 differentially expressed proteins were identified in centenarians compared to younger and geriatric groups.
- 37 proteins showed a 'younger' profile in centenarians, linked to immune, metabolic, and extracellular matrix pathways.
- Findings were validated using independent datasets NECS and TAME, confirming a consistent aging signature.

## Abstract

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.

We characterized the plasma proteomic profiles of centenarians from the SWISS100 cohort, identifying 583 differentially expressed proteins compared to younger and geriatric groups. Cross‐validation with the independent datasets NECS and the TAME consortium confirmed a robust aging signature, while fractional polynomial regressions revealed a specific subgroup of 37 proteins maintaining a “younger” profile in centenarians. These proteins implicate key pathways in longevity, including immune response, metabolic regulation, and extracellular matrix stability, offering potential targets for healthy aging.