Interrelations Between Mitochondrial DNA Copy Number and Inflammation in Older Adults

J Gerontol A Biol Sci Med Sci. 2017 Jul 1;72(7):937-944. doi: 10.1093/gerona/glx033.

Abstract

Background: Interplays between inflammation and mitochondrial biology are reported. Here, we examined the cross-sectional interrelationships of mitochondrial DNA copy number (mtDNACN) and inflammation and their interaction with physical functioning.

Methods: A total of 1990 community-dwelling adults aged 65 years and older who were participating in the Healthy Aging Longitudinal Study in Taiwan underwent measurements of peripheral-blood leukocytes MtDNACN, multiple inflammatory markers, grip strength, and gait speed.

Results: Principal components analysis revealed two inflammatory factors: factor 1 (high-sensitivity C-reactive protein [hs-CRP], white blood cell count, fibrinogen and interleukin-6 [IL-6]); factor 2 (tumor necrosis factor receptor 1, D-dimer and soluble interleukin-6 receptor). Participants with severe physical functioning impairment (low grip strength and gait speed) had higher (p < .05) levels of factor 1 and 2, but not mtDNACN, than did those with moderately impaired (low grip strength or gait speed) and normal physical functioning. MtDNACN was negatively related to factor 1 (r = -.221, p < .001) but not factor 2 (r = -.002, p = .938). Increased factor 1 was strongly associated with higher odds of physical functioning impairment in those with a low mtDNACN (adjusted odds ratios [OR] of moderate physical function impairment 1.21, 95% CI 1.01-1.44; adjusted OR of severe physical function impairment 1.52, 95% CI 1.25-1.85) but not in those with a high mtDNACN (p for interaction = .016).

Conclusions: A low mtDNACN was associated with an inflammation exhibiting elevated hs-CRP, IL-6, fibrinogen, and white blood cell count, and strengthened the association of this inflammation with physical functioning impairment.

Keywords: Aging; Biological markers/blood; Gait; Geriatric assessment; Muscle strength.

MeSH terms

  • Aged
  • Aging / physiology*
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • DNA Copy Number Variations*
  • DNA, Mitochondrial / genetics*
  • Female
  • Hand Strength / physiology
  • Humans
  • Inflammation* / blood
  • Inflammation* / pathology
  • Inflammation* / physiopathology
  • Interleukin-6 / blood
  • Leukocyte Count / methods
  • Leukocytes / metabolism*
  • Male
  • Mitochondria / genetics*
  • Physical Fitness / physiology*
  • Statistics as Topic
  • Taiwan
  • Walking Speed / physiology

Substances

  • Biomarkers
  • DNA, Mitochondrial
  • Interleukin-6
  • C-Reactive Protein