title: Polymorphisms in the mitochondrial DNA control region and frailty in older adults.
abstract: BACKGROUND
  Mitochondria contribute to the dynamics of cellular metabolism, the production of reactive oxygen species, and apoptotic pathways. Consequently, mitochondrial function has been hypothesized to influence functional decline and vulnerability to disease in later life. Mitochondrial genetic variation may contribute to altered susceptibility to the frailty syndrome in older adults.
  
  
  RESULTS
  To assess potential mitochondrial genetic contributions to the likelihood of frailty, mitochondrial DNA (mtDNA) variation was compared in frail and non-frail older adults. Associations of selected SNPs with a muscle strength phenotype were also explored. Participants were selected from the Cardiovascular Health Study (CHS), a population-based observational study (1989-1990, 1992-1993). At baseline, frailty was identified as the presence of three or more of five indicators (weakness, slowness, shrinking, low physical activity, and exhaustion). mtDNA variation was assessed in a pilot study, including 315 individuals selected as extremes of the frailty phenotype, using an oligonucleotide sequencing microarray based on the Revised Cambridge Reference Sequence. Three mtDNA SNPs were statistically significantly associated with frailty across all pilot participants or in sex-stratified comparisons: mt146, mt204, and mt228. In addition to pilot participants, 4,459 additional men and women with frailty classifications, and an overlapping subset of 4,453 individuals with grip strength measurements, were included in the study population genotyped at mt204 and mt228. In the study population, the mt204 C allele was associated with greater likelihood of frailty (adjusted odds ratio = 2.04, 95% CI = 1.07-3.60, p = 0.020) and lower grip strength (adjusted coefficient = -2.04, 95% CI = -3.33- -0.74, p = 0.002).
  
  
  CONCLUSIONS
  This study supports a role for mitochondrial genetic variation in the frailty syndrome and later life muscle strength, demonstrating the importance of the mitochondrial genome in complex geriatric phenotypes.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Ann Z
authors.initials: AZ
authors.lastname: Moore
authors.forename: Mary L
authors.initials: ML
authors.lastname: Biggs
authors.forename: Amy
authors.initials: A
authors.lastname: Matteini
authors.forename: Ashley
authors.initials: A
authors.lastname: O'Connor
authors.forename: Sarah
authors.initials: S
authors.lastname: McGuire
authors.forename: Brock A
authors.initials: BA
authors.lastname: Beamer
authors.forename: M Danielle
authors.initials: MD
authors.lastname: Fallin
authors.forename: Linda P
authors.initials: LP
authors.lastname: Fried
authors.forename: Jeremy
authors.initials: J
authors.lastname: Walston
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.forename: Dan E
authors.initials: DE
authors.lastname: Arking
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D016330:Frail Elderly; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic
chemical_list: D004272:DNA, Mitochondrial