High-throughput sequencing analysis of nuclear-encoded mitochondrial genes reveals a genetic signature of human longevity.

Autor: Gonzalez, Brenda, Tare, Archana, Ryu, Seungjin, Johnson, Simon C., Atzmon, Gil, Barzilai, Nir, Kaeberlein, Matt, Suh, Yousin
Předmět:
Zdroj: GeroScience; Feb2023, Vol. 45 Issue 1, p311-330, 20p
Abstrakt: Mitochondrial dysfunction is a well-known contributor to aging and age-related diseases. The precise mechanisms through which mitochondria impact human lifespan, however, remain unclear. We hypothesize that humans with exceptional longevity harbor rare variants in nuclear-encoded mitochondrial genes (mitonuclear genes) that confer resistance against age-related mitochondrial dysfunction. Here we report an integrated functional genomics study to identify rare functional variants in ~ 660 mitonuclear candidate genes discovered by target capture sequencing analysis of 496 centenarians and 572 controls of Ashkenazi Jewish descent. We identify and prioritize longevity-associated variants, genes, and mitochondrial pathways that are enriched with rare variants. We provide functional gene variants such as those in MTOR (Y2396Lfs*29), CPS1 (T1406N), and MFN2 (G548*) as well as LRPPRC (S1378G) that is predicted to affect mitochondrial translation. Taken together, our results suggest a functional role for specific mitonuclear genes and pathways in human longevity. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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