A Plasma Proteomic Signature Links Secretome of Senescent Monocytes to Aging- and Obesity-related Clinical Outcomes in Humans

Overview

Journal medRxiv

Date 2024 Oct 7

PMID 39371126

Authors

Bradley Olinger

Reema Banarjee

Amit Dey

Dimitrios Tsitsipatis

Toshiko Tanaka

Anjana Ram

Thedoe Nyunt

Gulzar Daya

Zhongsheng Peng

Linna Cui

Julian Candia

Eleanor M Simonsick

Myriam Gorospe

Keenan A Walker

Luigi Ferrucci

Nathan Basisty

Affiliations

Soon will be listed here.

Abstract

Cellular senescence increases with age and contributes to age-related declines and pathologies. We identified circulating biomarkers of senescence associated with diverse clinical traits in humans to facilitate future non-invasive assessment of individual senescence burden and efficacy testing of novel senotherapeutics. Using a novel nanoparticle-based proteomic workflow, we profiled the senescence-associated secretory phenotype (SASP) in monocytes and examined these proteins in plasma samples (N = 1060) from the Baltimore Longitudinal Study of Aging (BLSA). Machine learning models trained on monocyte SASP associated with several age-related phenotypes in a test cohort, including body fat composition, blood lipids, inflammation, and mobility-related traits, among others. Notably, a subset of SASP-based predictions, including a 'high impact' SASP panel that predicts age- and obesity-related clinical traits, were validated in InCHIANTI, an independent aging cohort. These results demonstrate the clinical relevance of the circulating SASP and identify relevant biomarkers of senescence that could inform future clinical studies.

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