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Association of heat shock proteins with all-cause mortality.
Monday,2013-09-30 15:11 America/Los_Angeles — poolea2
| Title | Association of heat shock proteins with all-cause mortality. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | 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 |
| Journal | Age (Dordr) |
| Volume | 35 |
| Issue | 4 |
| Pagination | 1367-76 |
| Date Published | 2013 Aug |
| ISSN | 1574-4647 |
| Keywords | Aged, 80 and over, Aging, Cause of Death, Forecasting, Genotype, Heat-Shock Proteins, Humans, Longevity, Promoter Regions, Genetic, Retrospective Studies, Transcription, Genetic, United States |
| Abstract | <p>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.</p> |
| DOI | 10.1007/s11357-012-9417-7 |
| Alternate Journal | Age (Dordr) |
| PubMed ID | 22555621 |
| PubMed Central ID | PMC3705092 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States M01-RR00425 / RR / NCRR NIH HHS / United States 1R03AG032498-01 / AG / NIA NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States R01 NS017950 / NS / NINDS NIH HHS / United States N01AG12100 / AG / NIA NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States R01 MD009164 / MD / NIMHD NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States 263 MD 821336 / MD / NIMHD NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States AG033193 / AG / NIA NIH HHS / United States 1R01AG032098-01A1 / AG / NIA NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01 AG062106 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States NS17950 / NS / NINDS NIH HHS / United States R01 AR041398 / AR / NIAMS NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268200782096C / HG / NHGRI NIH HHS / United States / / Intramural NIH HHS / United States R01 AG008122 / AG / NIA NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States AG031890 / AG / NIA NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States P30AG013846 / AG / NIA NIH HHS / United States N01 AG062103 / AG / NIA NIH HHS / United States R01 AG029451 / AG / NIA NIH HHS / United States N01-HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States R03 AG032498 / AG / NIA NIH HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States AG081220 / AG / NIA NIH HHS / United States R01AG029451 / AG / NIA NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States HHSN268200782096C / / PHS HHS / United States AR/AG 41398 / AG / NIA NIH HHS / United States 1R01AG028321 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States R01 AG028321 / AG / NIA NIH HHS / United States 263 MD 9164 / MD / NIMHD NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States R01 AG031890 / AG / NIA NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States |