Proteomic assessment of serum biomarkers of longevity in older men

• Published in: Aging cell Vol. 19; no. 11; pp. e13253 - n/a
• Main Authors: Orwoll, Eric S., Wiedrick, Jack, Nielson, Carrie M., Jacobs, Jon, Baker, Erin S., Piehowski, Paul, Petyuk, Vladislav, Gao, Yuqian, Shi, Tujin, Smith, Richard D., Bauer, Douglas C., Cummings, Steven R., Lapidus, Jodi
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-11-2020; Anatomical Society - Wiley; John Wiley and Sons Inc
• Subjects: 60 APPLIED LIFE SCIENCES; Age; Aged; Aging; Antigens; Biological markers; biomarker; Biomarkers; Biomarkers - blood; Comparative analysis; Complement activation; Humans; Immunoglobulins; inflammation; Life span; Liquid chromatography; Longevity; Longitudinal studies; Male; Mass spectrometry; Mass spectroscopy; men; Original; Original Paper; Peptides; Proteins; Proteomics; Proteomics - methods; longevity; aging; proteomics; biomarker; inflammation; men
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.13253

The biological bases of longevity are not well understood, and there are limited biomarkers for the prediction of long life. We used a high‐throughput, discovery‐based proteomics approach to identify serum peptides and proteins that were associated with the attainment of longevity in a longitudinal study of community‐dwelling men age ≥65 years. Baseline serum in 1196 men were analyzed using liquid chromatography–ion mobility–mass spectrometry, and lifespan was determined during ~12 years of follow‐up. Men who achieved longevity (≥90% expected survival) were compared to those who died earlier. Rigorous statistical methods that controlled for false positivity were utilized to identify 25 proteins that were associated with longevity. All these proteins were in lower abundance in long‐lived men and included a variety involved in inflammation or complement activation. Lower levels of longevity‐associated proteins were also associated with better health status, but as time to death shortened, levels of these proteins increased. Pathway analyses implicated a number of compounds as important upstream regulators of the proteins and implicated shared networks that underlie the observed associations with longevity. Overall, these results suggest that complex pathways, prominently including inflammation, are linked to the likelihood of attaining longevity. This work may serve to identify novel biomarkers for longevity and to understand the biology underlying lifespan.
In a cohort of older men, discovery‐based serum proteomics at baseline revealed protein biomarkers that were robustly associated with the achievement of longevity during ~12 years of subsequent follow‐up. Longevity‐associated proteins were frequently associated with inflammatory pathways.