Inherited Variability of the Mitochondrial Genome and Successful Aging in Humans

Abstract

Increasing data indicate that polymorphic variants of nuclear loci can affect rate and quality of aging in humans. However, the mitochondrial genome is another good candidate, because of the central role played by mitochondrial genes in oxidative phosphorylation (OXPHOS) and cell metabolism. A characteristic of the mitochondrial genome (mtDNA) is the high level of interindividual variability that ensues from high mutation rate and unilinear inheritance. Related groups of germline/inherited mtDNA polymorphisms (haplogroups) have been identified as continent‐specific sets of stable/ancient/associated restriction fragment length polymorphisms in the mtDNA coding region, representing markers capable of exactly depicting the mtDNA pool of a specific population. The hypothesis can be put forward that mtDNA variants included in a haplogroup may have similar OXPHOS efficiency and therefore act as genetic factors predisposing to individual successful or unsuccessful aging. This idea can be explored by sampling groups of individuals of different ages from a well‐defined population and comparing the pools of mtDNA haplogroups between samples. The results obtained by screening mtDNA haplogroups in about 800 Italians of different ages, including more that 200 centenarians, agree with the hypothesis that the inherited variability of the mitochondrial genome is associated with the chance of successful aging and longevity in humans.

Mitochondrial Genetic Background Modifies Breast Cancer Risk

“…As a matter of fact, contradictory results on haplogroup J and disease association have been reported. An association between haplogroup J and longevity in Northern Italian men was found (47,48). Conversely, haplogroup J has also been found to increase the risk for disease expression of Leber's hereditary optic neuropathy (6).…”

Comparison of telomere length between population-specific mitochondrial haplogroups among different age groups in a Latvian population

“…Numerous studies have observed that hg J is more abundant among centenarians, while hg U decreases among centenarians (de Benedictis et al, 1999;Rose et al, 2001) suggested that longevity is population-specific (Pinós et al, 2012). On the other hand several other studies have failed to find an association of longevity with hgs H and U (de Benedictis et al, 1999;de Benedictis et al, 2000;Pinós et al, 2012). A study by Benn et al also concludes that there are no hg associations with mortality and longevity (Benn et al, 2008).…”

APOE4, oxidative stress and decreased repair capacity - a no-brainer. Faulty lipid metabolism and increased levels of oxidative damage may be risk factors in the pathogenesis of late-onset dementia

“…Sub-haplogroup N9a has also been found to protect its carriers from diabetes type 2 and metabolic syndrome [109] therefore, the protective effects against adverse outcomes after stroke may have been indirect. Mitochondrial haplogroups J, U, K and T and the unrelated haplogroup X were consistently seen more commonly in healthy individuals over 90 than in the healthy 'younger old' [95,110,111]. Carriership of haplogroup K (common in Western Europe and the British Islands) may protect against transient ischaemic attack and ischemic stroke [112].…”

“…More than 15 currently existing haplogroups of mitochondrial DNA have been described [93,94]. Different mitochondrial haplogroups may be associated with varying efficiency of oxygen utilisation [95]. Generally, the higher the oxygen consumption, the higher amount of ATP synthesised, and, respectively, the higher the levels of ROS and the daily amount of oxidative damage to DNA.…”