Lifestyle and behavioral factors and mitochondrial DNA copy number in a diverse cohort of mid-life and older adults

Abstract

Mitochondrial DNA copy number (mtDNAcn) is a putative biomarker of oxidative stress and biological aging. Modifiable factors, including physical activity (PA), avoidance of heavy alcohol use and smoking, and maintaining good mental health, may reduce oxidative stress and promote healthy aging. Yet, limited data exist regarding how these factors are associated with mtDNAcn or whether age, sex or race/ethnicity moderate associations. In this cross-sectional study, we selected 391 adults (183 non-Hispanic White, 110 Black and 98 Hispanic; mean = 67 years) from the VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention) ancillary to the VITAL trial. We estimated associations between lifestyle and behavioral factors (PA, alcohol consumption, cigarette smoking and depression) and log-transformed mtDNAcn using multivariable linear regression models. MtDNAcn was not correlated with chronological age; women had ~17% higher mtDNAcn compared to men. There were no significant associations between PA measures (frequency, amount or intensity) or alcohol consumption with mtDNAcn. Cigarette smoking (per 5 pack-years) was significantly associated with mtDNAcn (percent difference = -2.9% (95% confidence interval (CI) = -5.4%, -0.4%)); a large contrast was observed among heavy vs. non-smokers (≥30 vs. 0 pack-years): percent difference = -28.5% (95% CI = -44.2%, -8.3%). The estimate of mtDNAcn was suggestively different for past vs. no depression history (percent difference = -15.1% 95% CI = -30.8%, 4.1%), but this difference was not statistically significant. The association between smoking and log-mtDNAcn varied by sex and race/ethnicity; it was stronger in men and Black participants. While chance findings cannot be excluded, results from this study support associations of smoking, but not chronological age, with mtDNAcn and suggest nuanced considerations of mtDNAcn as indicative of varying oxidative stress states vs. biological aging itself.

Genetic polymorphisms of metabolic enzyme genes associated with leukocyte mitochondrial DNA copy number in PAHs exposure workers

“…What's more, the GLM indicated that the male may be a risk factor of the decreased mtDNAcn [ β (95% CI) = −0.058 (−0.103, −0.012), p = .013]. Vyas et al 25 found that female has higher mtDNAcn compared to male in a diverse cohort of mid‐life and older adults. Yu et al 26 observed the same gender‐specific phenomenon in a cross‐sectional analysis.…”

Genetic analysis of mitochondrial DNA copy number and associated traits identifies loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation, and reveals a causal association of mitochondrial function with mortality

“…A role for apoptosis, and specifically BCL2 , in proplatelet formation and platelet release has been suggested 92,93 , however work in mice has suggested that apoptosis does not play a direct role in these processes 94 . Nevertheless, apoptosis is important for platelet lifespan 95 .…”

Mitochondria-DNA copy-number and incident venous thromboembolism among middle-aged women: a population-based cohort study

“…Due to limited study size, we may not exclude minor associations. The level of mtDNA-CN is determined by heredity, in addition to the influence on one's lifestyle habits such as physical activity, smoking, and alcohol consumption [21][22][23][24][25]35]. Poor self-rated health is also associated with low levels of mtDNA-CN [19].…”

“…Poor self-rated health is also a predictor for incident CVD [ 20 ]. Lifestyle may also affect the levels of mtDNA-CN; current smoking is associated with lower amount of mtDNA-CN [ 21 ] and studies have suggested that high alcohol consumption may affect the levels of mtDNA-CN [ 22 , 23 ]. In contrast, healthy lifestyle, such as regular physical activity, is associated with higher mtDNA-CN [ 24 , 25 ].…”