Association of heat shock proteins with all-cause mortality

L. Broer, E. W. Demerath, M. E. Garcia, G. Homuth, Robert C. Kaplan, K. L. Lunetta, T. Tanaka, G. J. Tranah, S. Walter, A. M. Arnold, G. Atzmon, T. B. Harris, W. Hoffmann, D. Karasik, D. P. Kiel, T. Kocher, L. J. Launer, K. K. Lohman, J. I. Rotter, H. TiemeierA. G. Uitterlinden, H. Wallaschofski, S. Bandinelli, M. Dörr, L. Ferrucci, N. Franceschini, V. Gudnason, A. Hofman, Y. Liu, J. M. Murabito, A. B. Newman, B. A. Oostra, B. M. Psaty, A. V. Smith, C. M. Van Duijn

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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-causemortality. Rs1416733 is a known ciseQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.

Original languageEnglish (US)
Pages (from-to)1367-1376
Number of pages10
JournalAge
Volume35
Issue number4
DOIs
StatePublished - Aug 2013

Fingerprint

Heat-Shock Proteins
Shock
Hot Temperature
Single Nucleotide Polymorphism
Mortality
Cell Death
Small Heat-Shock Proteins
HSP70 Heat-Shock Proteins
Population
Genes
Proteins

Keywords

  • All-cause mortality
  • Heat shock proteins
  • Heatshock factor 2

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology
  • Medicine(all)

Cite this

Broer, L., Demerath, E. W., Garcia, M. E., Homuth, G., Kaplan, R. C., Lunetta, K. L., ... Van Duijn, C. M. (2013). Association of heat shock proteins with all-cause mortality. Age, 35(4), 1367-1376. https://doi.org/10.1007/s11357-012-9417-7

Association of heat shock proteins with all-cause mortality. / Broer, L.; Demerath, E. W.; Garcia, M. E.; Homuth, G.; Kaplan, Robert C.; Lunetta, K. L.; Tanaka, T.; Tranah, G. J.; Walter, S.; Arnold, A. M.; Atzmon, G.; Harris, T. B.; Hoffmann, W.; Karasik, D.; Kiel, D. P.; Kocher, T.; Launer, L. J.; Lohman, K. K.; Rotter, J. I.; Tiemeier, H.; Uitterlinden, A. G.; Wallaschofski, H.; Bandinelli, S.; Dörr, M.; Ferrucci, L.; Franceschini, N.; Gudnason, V.; Hofman, A.; Liu, Y.; Murabito, J. M.; Newman, A. B.; Oostra, B. A.; Psaty, B. M.; Smith, A. V.; Van Duijn, C. M.

In: Age, Vol. 35, No. 4, 08.2013, p. 1367-1376.

Research output: Contribution to journalArticle

Broer, L, Demerath, EW, Garcia, ME, Homuth, G, Kaplan, RC, Lunetta, KL, Tanaka, T, Tranah, GJ, Walter, S, Arnold, AM, Atzmon, G, Harris, TB, Hoffmann, W, Karasik, D, Kiel, DP, Kocher, T, Launer, LJ, Lohman, KK, Rotter, JI, Tiemeier, H, Uitterlinden, AG, Wallaschofski, H, Bandinelli, S, Dörr, M, Ferrucci, L, Franceschini, N, Gudnason, V, Hofman, A, Liu, Y, Murabito, JM, Newman, AB, Oostra, BA, Psaty, BM, Smith, AV & Van Duijn, CM 2013, 'Association of heat shock proteins with all-cause mortality', Age, vol. 35, no. 4, pp. 1367-1376. https://doi.org/10.1007/s11357-012-9417-7
Broer L, Demerath EW, Garcia ME, Homuth G, Kaplan RC, Lunetta KL et al. Association of heat shock proteins with all-cause mortality. Age. 2013 Aug;35(4):1367-1376. https://doi.org/10.1007/s11357-012-9417-7
Broer, L. ; Demerath, E. W. ; Garcia, M. E. ; Homuth, G. ; Kaplan, Robert C. ; Lunetta, K. L. ; Tanaka, T. ; Tranah, G. J. ; Walter, S. ; Arnold, A. M. ; Atzmon, G. ; Harris, T. B. ; Hoffmann, W. ; Karasik, D. ; Kiel, D. P. ; Kocher, T. ; Launer, L. J. ; Lohman, K. K. ; Rotter, J. I. ; Tiemeier, H. ; Uitterlinden, A. G. ; Wallaschofski, H. ; Bandinelli, S. ; Dörr, M. ; Ferrucci, L. ; Franceschini, N. ; Gudnason, V. ; Hofman, A. ; Liu, Y. ; Murabito, J. M. ; Newman, A. B. ; Oostra, B. A. ; Psaty, B. M. ; Smith, A. V. ; Van Duijn, C. M. / Association of heat shock proteins with all-cause mortality. In: Age. 2013 ; Vol. 35, No. 4. pp. 1367-1376.
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AU - Garcia, M. E.

AU - Homuth, G.

AU - Kaplan, Robert C.

AU - Lunetta, K. L.

AU - Tanaka, T.

AU - Tranah, G. J.

AU - Walter, S.

AU - Arnold, A. M.

AU - Atzmon, G.

AU - Harris, T. B.

AU - Hoffmann, W.

AU - Karasik, D.

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AU - Launer, L. J.

AU - Lohman, K. K.

AU - Rotter, J. I.

AU - Tiemeier, H.

AU - Uitterlinden, A. G.

AU - Wallaschofski, H.

AU - Bandinelli, S.

AU - Dörr, M.

AU - Ferrucci, L.

AU - Franceschini, N.

AU - Gudnason, V.

AU - Hofman, A.

AU - Liu, Y.

AU - Murabito, J. M.

AU - Newman, A. B.

AU - Oostra, B. A.

AU - Psaty, B. M.

AU - Smith, A. V.

AU - Van Duijn, C. M.

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