Dataset Information

Proteomic assessment of serum biomarkers of longevity in older men

ABSTRACT: We utilized a high throughput discovery-based proteomics platform 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 or older. 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.

INSTRUMENT(S): LTQ Orbitrap XL

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Eric Orwoll

PROVIDER: MSV000085611 | MassIVE | Fri Jun 19 00:00:00 BST 2020

REPOSITORIES: MassIVE

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Publications

High-throughput serum proteomics for the identification of protein biomarkers of mortality in older men.

Orwoll Eric S ES Wiedrick Jack J 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 Nielson Carrie M CM Lapidus Jodi J

Aging cell 20180205 2

The biological perturbations associated with incident mortality are not well elucidated, and there are limited biomarkers for the prediction of mortality. We used a novel high-throughput proteomics approach to identify serum peptides and proteins associated with 5-year mortality in community-dwelling men age ≥65 years who participated in a longitudinal observational study of musculoskeletal aging (Osteoporotic Fractures in Men: MrOS). In a discovery phase, serum specimens collected at baseline i ...[more]

PMID: 29399943

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Project description:Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan. Two independent replicates were performed. Total RNA was extracted with TRIzol (Invitrogen). The extracted RNA was purified with PureLink RNA Micro Kit (Invitrogen) and analyzed with Agilent 2100 Bioanalyzer to assess the RNA integrity. The microarray procedures were performed according to Affymetrix protocols. Hybridized arrays were scanned using an Affymetrix GeneChip Scanner.