The gene sirtuin 6 has been found to be responsible for more efficient DNA repair in species with longer lifespans, findings illuminate new targets for anti-aging research and interventions that may help to prevent age related diseases.
With age human and mammal DNA becomes increasingly prone to breaks that can lead to gene rearrangements, mutations, as well as hallmarks of cancer and aging. DNA repair has been hypothesized to play an important role in determining lifespan of an organism for that reason. Behaviors such as smoking can exacerbate double strand breaks in DNA, but breaks are unavoidable even if super extra healthy, one of the main causes of double strand breaks is oxidative damage and since oxygen is needed to breathe these breaks are inevitable.
Smaller organisms such as mice have less chance of accumulating double strand breaks due to their comparatively short lives vs those with longer lifespans, but to live for 50 years or so a system needs to be in place to fix these breaks.
Due to roles in organizing proteins and recruiting enzymes that repair broken DNA the gene sirtuin 6 is often referred to as the longevity gene; studies have shown mice without this gene age prematurely while those with extra copies live longer. Based on this more efficient DNA repair is hypothesized to be required for longer lifespans therefore organisms may have evolved with more efficient DNA repair regulators. Does this mean that SIRT6 activity is enhanced in species with longer lifespans?
18 rodent species with lifespans ranging from 3 years to 32 years DNA was analyzed to test this theory. Rodents with longer lifespans were found to experience more efficient DNA repair because products of their SIRT6 gene were more potent, and SIRT6 was not the same in every species; SIRT6 appears to have co-evolved with longevity to become more efficient making the species with stronger SIRT6 genes live longer.
“The SIRT6 protein seems to be the dominant determinant of lifespan,” Professor Dirk Bohmann says. “We show that at the cell level, the DNA repair works better, and at the organism level, there is an extended lifespan.”
Molecular differences between SIRT6 found in mice were analyzed against proteins found in beavers; 5 amino acids were identified responsible for making stronger beaver SIRT6 proteins which were more active in repairing DNA and better at enzyme functions. When beaver and mouse SIRT6 proteins were inserted into human cells the beaver proteins better reduced stress induces DNA damage compared to mice proteins, and beaver proteins increased lifespan of fruit flies better than mouse SIRT6 proteins.
Human SIRT6 appears to already be optimized to function, next step is to analyze whether or not other species such as the bowhead whale which can live 200+ years have evolved even more robust SIRT6 genes.
“The ultimate goal is to prevent age-related diseases in humans,” Professor Vera Gorbunova says. “If diseases happen because of DNA that becomes disorganized with age, we can use research like this to target interventions that can delay cancer and other degenerative diseases.”
