Genetics of aging
A decade after Johnson's discovery daf-2, one of the two genes that are essential for dauer larva formation,[3] was shown by Cynthia Kenyon to double C. elegans lifespan.
Subsequent genetic modification (PI3K-null mutation) to C. elegans was shown to extend maximum life span tenfold.
[7] Knockdown of the nucleotide excision repair gene Xpa-1 increased sensitivity to UV and reduced the life span of the long-lived mutants.
[10]) Whether the Sir2 homologues in higher organisms have any role in lifespan is unclear, but the human SIRT1 protein has been demonstrated to deacetylate p53, Ku70, and the forkhead family of transcription factors.
Superoxide dismutase, a protein that protects against the effects of mitochondrial free radicals, can extend yeast lifespan in stationary phase when overexpressed.
Mutations that affect insulin-like signaling in worms, flies, and the growth hormone/IGF1 axis in mice are associated with extended lifespan.
[11] The following is a list of genes connected to longevity through research [11] on model organisms: In July 2020 scientists, using public biological data on 1.75 m people with known lifespans overall, identify 10 genomic loci which appear to intrinsically influence healthspan, lifespan, and longevity – of which half have not been reported previously at genome-wide significance and most being associated with cardiovascular disease – and identify haem metabolism as a promising candidate for further research within the field.
[15] In the absence of senescent cells, the mice's tissues showed a major improvement in the usual burden of age-related disorders.
A second study led by Jan van Deursen in collaboration with a team of collaborators at the Mayo Clinic and Groningen University, provided the first direct in vivo evidence that cellular senescence causes signs of aging by eliminating senescent cells from progeroid mice by introducing a drug-inducible suicide gene and then treating the mice with the drug to kill senescent cells selectively, as opposed to decreasing whole body p16.
[17] The genetically determined capability to repair DNA damage appears to be a key aging factor in comparisons of several species of birds and animals.
When the rate of accumulation of DNA damage (double-strand breaks) in the leukocytes of dolphins, goats, reindeer, American flamingos, and griffon vultures was compared to the longevity of individuals of these different species, it was found that the species with longer lifespans have slower accumulation of DNA damage.
Lymphoblastoid cell lines established from blood samples of humans who lived past 100 years (centenarians) were found to have a significantly higher activity of the DNA repair protein Poly (ADP-ribose) polymerase (PARP) than cell lines from younger individuals (20 to 70 years old).
[22] The researchers also found a correlation between paternal age and offspring death by injury or poisoning, indicating the need to control for social and behavioral confounding factors.
