Contributions of inherited mtDNA to longevity: evidence from extended pedigrees with 176 million kinship pairs.
Level 3 - non-randomized controlled study
Retrospective genealogical cohort study analyzing kinship pairs
PubMed 40907250 · doi:10.1016/j.ebiom.2025.105911
What was done
Analyzed genealogical records from the Utah Population Database (UPDB) covering 1,018,929 individuals born between 1700 and 1925, comprising 176,348,110 unique kinship pairs across 1st to 5th degree relatives. Longevity was defined as surviving into the top 10% of one's birth cohort. Investigators compared matrilineal versus patrilineal relatedness using variance component analyses to quantify the heritability contribution of mtDNA relative to nuclear DNA.
What was found
Matrilineal relatives showed greater similarity in longevity outcomes than non-maternal relatives across 1st through 5th degree kin. Nuclear DNA heritability was 23% to 26%, whereas mtDNA heritability was at least 5%. Sharing the maternal lineage of a longevous relative was associated with an average lifespan increase of 11.3 months.
Why it matters
This study provides large-scale population evidence quantifying the contribution of inherited mitochondrial DNA to human lifespan, showing that mtDNA heritability accounts for meaningful variation in exceptional longevity independent of nuclear genetics.
Limits
The study is based on a historical Utah cohort (1700–1925), which may limit generalizability to genetically diverse modern populations. Genealogical models cannot completely separate mtDNA sequence variants from non-genetic maternal effects, intrauterine environment, or matrilineally shared culture and microbiome. Direct mtDNA sequencing was not conducted to identify causal variants.