Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

Experimental mild heat shock is widely known as an intervention that results in extended longevity in various models along the evolutionary lineage. Heat shock proteins (HSPs) are highly upregulated immediately after a heat shock. The elevation in HSP levels was shown to inhibit stress-mediated cell death, and recent experiments indicate a highly versatile role for these proteins as inhibitors of programmed cell death. In this study, we examined common genetic variations in 31 genes encoding all members of the HSP70, small HSP, and heat shock factor (HSF) families for their association with all-cause mortality. Our discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged 55 years and older (3,174 deaths). We assessed 4,430 single nucleotide polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. After adjusting for multiple testing by permutation analysis, three SNPs showed evidence for association with all-cause mortality in RS1. These findings were followed in eight independent population-based cohorts, leading to a total of 25,007 participants (8,444 deaths). In the replication phase, only HSF2 (rs1416733) remained significantly associated with all-cause mortality. Rs1416733 is a known cis-eQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.

Original publication

DOI

10.1007/s11357-012-9417-7

Type

Journal article

Journal

Age (Dordrecht, Netherlands)

Publication Date

08/2013

Volume

35

Pages

1367 - 1376

Addresses

Department of Epidemiology, Erasmus Medical Center, Dr. Molewaterplein 50, PO-Box 2040, 3000, CA, Rotterdam, The Netherlands.

Keywords

Humans, Heat-Shock Proteins, Cause of Death, Retrospective Studies, Transcription, Genetic, Aging, Longevity, Genotype, Forecasting, Aged, 80 and over, United States, Promoter Regions, Genetic