A new gene associated with longevity has been uncovered. A group of Chinese researchers have functionally validated the non-mitochondria-targeted nuclear gene, CG11837, which is conserved across animals, as having an effect on rate of aging. They also found a human gene, gene DIMT1, which is a 93 percent match with it.
CG11837 exhibited strong evolutionary rate covariation (ERC) with mtOXPHOS genes and severely affected mitochondrial morphology. Knockdown of CG11837 shortened lifespans in six diverse organisms, and overexpression increased lifespan in fruit fly and worm.
The study was published June 4 in the journal Nature Aging. The lead author is Mei Tao of the Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province.
Oxidative phosphorylation is essential for energy metabolism, linked to the regulation of longevity, and involves mitochondrial and nuclear genes. “The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied, but little is known about whether other nuclear genes not targeted to mitochondria evolutionarily and functionally interact with mitochondrial genes,” these authors write.
This team systematically examined the ERC of mitochondrial and nuclear benchmarking universal single-copy ortholog (BUSCO) genes from 472 insects, identifying 75 non-mitochondria-targeted nuclear genes. To find these genes, the team looked at 1,283 DNA segments in insects, before finding an uncharacterized CG11837 gene that regulates their lifespan.
They found that single gene—CG11837—determines whether certain insects die young: Its knockdown reduces median lifespan in five diverse insect species and the worm Caenorhabditis elegans (C. elegans), whereas its overexpression extends median lifespans in fruit flies and C. elegans and enhances oxidative phosphorylation gene activity. These data provide insights into the ERC of mito-nuclear genes and suggest that CG11837 may regulate longevity across animals. When researchers increased activity of the gene, the fruit flies lived up to 59 percent more.
Given the increased lifespan with CG11837 overexpression, the team analyzed the correlation between CG11837 gene expression levels and lifespans from 43 insects representing nine orders. They found that relative expression levels of CG11837 were significantly positively correlated with their lifespan.
The researchers also ran the gene through a human database and found a 93 percent match with the human gene DIMT1. Both DIMT1 and CG11837 alter mitochondria, and thus play a role in balancing oxidation stress that drives the aging process. Mitochondria produce the ATP cells need to function.
The team performed in vitro studies using human cells that produced more DIMT1. The modified cells grew at the same rate as unaltered ones, but when the team exposed both groups to X-rays, which damages cells, they found a difference. In lab studies, they exposed human cells to radiation to cause damage that is somewhat comparable to age-related degradation that happens in people. They found the cells that had a ramped up DIMT1 gene “aged” 65 percent slower than the unaltered cells.
The researchers write, “Many longevity-promoting genes have been reported across species from fungi to mammals. For example, Sir2, a member of the Sirtuin family, has been reported to promote longevity in yeast. However, studies on the effects of Sir2 on lifespan extension in worms and flies have yielded conflicting results.”
