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Association of mitochondrial DNA levels with frailty and all-cause mortality.
Wednesday,2015-03-04 11:52 America/Los_Angeles — zdrager
| Title | Association of mitochondrial DNA levels with frailty and all-cause mortality. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Ashar, FN, Moes, A, Moore, AZ, Grove, ML, Chaves, PHM, Coresh, J, Newman, AB, Matteini, AM, Bandeen-Roche, K, Boerwinkle, E, Walston, JD, Arking, DE |
| Journal | J Mol Med (Berl) |
| Volume | 93 |
| Issue | 2 |
| Pagination | 177-186 |
| Date Published | 2015 Feb |
| ISSN | 1432-1440 |
| Keywords | African Americans, Aged, Aged, 80 and over, Aging, DNA, Mitochondrial, European Continental Ancestry Group, Female, Follow-Up Studies, Gene Dosage, Geriatric Assessment, Humans, Kaplan-Meier Estimate, Male, Mortality, Odds Ratio, Population Surveillance, Prospective Studies, Surveys and Questionnaires, United States |
| Abstract | <p>Mitochondrial function is altered with age and variants in mitochondrial DNA (mtDNA) modulate risk for several age-related disease states. However, the association of mtDNA copy number, a readily available marker which reflects mitochondrial depletion, energy reserves, and oxidative stress, on aging and mortality in the general population has not been addressed. To assess the association between mtDNA copy number and two primary outcomes--prevalent frailty and all-cause mortality--we utilize data from participants who were from two multicenter, multiethnic, community-based, prospective studies--the Cardiovascular Health Study (CHS) (1989-2006) and the Atherosclerosis Risk in Communities (ARIC) study (1987-2013). A total of 4892 participants (43.3% men) from CHS and 11,509 participants (44.9% men) from ARIC self-identifying as white or black were included in the analysis. mtDNA copy number, the trait of interest, was measured using a qPCR-based method in CHS and an array-based method in ARIC from DNA isolated from whole blood in participants from both cohorts. In race-stratified meta-analyses, we observe a significant inverse association of mtDNA copy number with age and higher mtDNA copy number in women relative to men. Lower mtDNA copy number was also significantly associated with prevalent frailty in white participants from CHS (OR 0.91, 95% CI 0.85-0.97). Additionally, mtDNA copy number was a strong independent predictor of all-cause mortality in an age- and sex-adjusted, race-stratified analysis of 16,401 participants from both cohorts with a pooled hazard ratio of 1.47 (95% CI 1.33-1.62) for the lowest quintile of mtDNA copy number relative to the highest quintile. Key messages: Mitochondrial DNA (mtDNA) copy number is associated with age and sex. Lower mtDNA copy number is also associated with prevalent frailty. mtDNA copy number is a significant predictor of all-cause mortality in a multiethnic population.</p> |
| DOI | 10.1007/s00109-014-1233-3 |
| Alternate Journal | J. Mol. Med. |
| PubMed ID | 25471480 |
| PubMed Central ID | PMC4319988 |
| Grant List | UL1RR025005 / RR / NCRR NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States P30-AG021334 / AG / NIA NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States UL1 TR001079 / TR / NCATS NIH HHS / United States HHSN268201100005C / / PHS HHS / United States HHSN268201100009C / / PHS HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States P30 AG021334 / AG / NIA NIH HHS / United States HHSN268200625226C / / PHS HHS / United States HHSN268201100010C / / PHS HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States N01 HC085082 / HC / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01 HC085080 / HC / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States HHSN268201100008C / / PHS HHS / United States HHSN268201100012C / / PHS HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States HHSN268201100007C / / PHS HHS / United States HHSN268200800007C / / PHS HHS / United States HHSN268201100011C / / PHS HHS / United States HHSN268201200036C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States HHSN268201100006C / / PHS HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States N01 HC55222 / HC / NHLBI NIH HHS / United States |