Mitochondrial DNA involvement in human longevity

Abstract

The main message of this review can be summarized as follows: aging and longevity, as complex traits having a significant genetic component, likely depend on a number of nuclear gene variants interacting with mtDNA variability both inherited and somatic. We reviewed the data available in the literature with particular attention to human longevity, and argued that what we hypothesize for aging and longevity could have a more general relevance and be extended to other age-related complex traits such as Alzheimer's and Parkinson's diseases. The genetics which emerges for complex traits, including aging and longevity, is thus even more complicated than previously thought, as epistatic interactions between nuclear gene polymorphisms and mtDNA variability (both somatic and inherited) as well as between mtDNA somatic mutations (tissue specific) and mtDNA inherited variants (haplogroups and sub-haplogroups) must be considered as additional players capable of explaining a part of the aging and longevity phenotype. To test this hypothesis is one of the main challenge in the genetics of aging and longevity in the next future.

Demographic characteristics of Sardinian centenarian genealogies: Preliminary results of the AKeA2 study

“…We regard this result as very important, particularly in relation to the many results recently obtained in genetics. All the data collected in this and other studies suggest that, as well as a variety of nuclear DNA polymorphisms (Di Bona et al 2009;Gravina et al 2009;Invidia et al 2010;Lescai, Marchegiani, and Franceschi 2009;Salvioli et al 2006;Testa et al 2009), maternally inherited mitochondrial DNA variants (Capri et al 2008;Raule et al 2007;Rose et al 2007;Rose et al 2010;Santoro et al 2006) contribute substantially to human longevity too.…”

The champions' mitochondria: is it genetically determined? A review on mitochondrial DNA and elite athletic performance

“…Mitochondrial haplogroups can modulate mitochondrial metabolism (leading to mild differences in OXPHOS activity), and they could also affect the cross talk that exists between nuclear and mitochondrial genomes (65,66). Research on mouse cell lines with homogeneous nuclear genome and different mitochondrial haplogroups showed an effect of mitochondrial haplogroups on cell respiration and defenses against ROS (54).…”

“…They can influence spermatozoa motility (52,65) or the development of mitochondrial disorders (29). Mitochondrial haplogroups could also have an effect on human longevity, at least in some ethnic/geographical cohorts (18,38,56,63,64,66,75,83).…”

Can we optimise the exercise training prescription to maximise improvements in mitochondria function and content?

“…[86,87]. It has been suggested that mitochondrial haplogroups have the potential to modulate mitochondrial metabolism (leading to mild differences in OXPHOS activity), and hence may affect the training response [88].…”