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Proteomic assessment of serum biomarkers of longevity in older men.

ABSTRACT: 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.

SUBMITTER: Orwoll ES

PROVIDER: S-EPMC7681066 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Proteomic assessment of serum biomarkers of longevity in older men.

Orwoll Eric S ES Wiedrick Jack J Nielson Carrie M CM Jacobs Jon J Baker Erin S ES Piehowski Paul P Petyuk Vladislav V Gao Yuqian Y Shi Tujin T Smith Richard D RD Bauer Douglas C DC Cummings Steven R SR Lapidus Jodi J

Aging cell 20201020 11

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 foll ...[more]

PMID: 33078901

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Project description:BACKGROUND AND OBJECTIVES:Mild hyponatremia is a common finding in older adults; however, the association of lower serum sodium with cognition in older adults is currently unknown. We determined whether lower normal serum sodium is associated with cognitive impairment and risk of cognitive decline in community-dwelling older men. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Five thousand four hundred thirty-five community-dwelling men aged ?65 years who participated in Osteoporotic Fractures in Men, a cohort study with a median follow-up for cognitive function of 4.6 years, were included in this analysis. Multivariable logistic regression was used to examine the association between baseline fasting serum sodium levels and the odds of prevalent cognitive impairment (cross-sectional analysis; modified Mini-Mental Status [3MS] score <1.5 SD [<84] below or Trail Making Test Part B time >1.5 SD above the mean [>223 seconds]) and cognitive decline (prospective analysis [n=3611]; decrease in follow-up 3MS score or increase in Trails B time >1.5 SD of the mean score/time change [>9 or >67 seconds]). RESULTS:Participants were aged 74±6 years with a fasting mean serum sodium level of 141±3 mmol/L. Fifteen percent (n=274), 12% (n=225), and 13% (n=242) had prevalent cognitive impairment in tertiles 1, 2, and 3, respectively. After adjustment, lower serum sodium was associated with prevalent cognitive impairment (tertile 1 [126-140 mmol/L] versus tertile 2 [141-142 mmol/L], odds ratio [OR], 1.30; 95% confidence interval [95% CI], 1.06 to 1.61). Fourteen percent (n=159), 10% (n=125), and 13% (n=159) had cognitive decline in tertiles 1, 2, and 3, respectively. Lower serum sodium was also associated with cognitive decline (tertile 1 versus tertile 2, OR, 1.37; 95% CI, 1.06 to 1.77). Tertile 3 (143-153 mmol/L) was additionally associated with cognitive decline. Results were similar in sensitivity analyses according to clinical cut-offs and by quartiles. CONCLUSIONS:In community-dwelling older men, serum sodium between 126-140, and 126-140 or 143-153 mmol/L, are independently associated with prevalent cognitive impairment and cognitive decline, respectively.

Dataset Information

Proteomic assessment of serum biomarkers of longevity in older men.

Publications

Proteomic assessment of serum biomarkers of longevity in older men.

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