The Elixir of Longevity
For centuries people have been searching for ways to look and feel younger. While scientists haven’t exactly discovered a magical anti-aging potion, they have found SIRT6 genes that repairs broken DNA and can help us live longer and healthier lives.
For a long time, it has been hypothesized that DNA repair plays a key role in determining longevity, but until now there has been no specific evidence confirming these findings. Researchers at the University of Rochester have now discovered that the gene sirtuin 6 (SIRT6) is responsible for more efficient DNA repair in species with longer lifespans. This research may offer important insight into anti-aging interventions and the prevention of age-related diseases. The study, “SIRT6 Is Responsible for More Efficient DNA Double-Strand Break Repair in Long-Lived Species”, was recently published in the journal Cell.
DNA repair is linked to longevity
As human beings age, DNA is susceptible to damage and double-strand breaks (DSBs), meaning that both strands in the DNA helix are severed. These breaks can lead to gene chromosomal rearrangements and mutations, which not only bring about the effects of aging, but can cause several types of cancer. Behaviors such as smoking can intensify breakage, but breakage itself is unavoidable since it is caused by oxidative damage and humans require oxygen to live. DNA repair acts in processes to correct DNA breakage and, for this reason, has long been considered essential in determining how long an organism can live.
DNA repair is possible with the help of sirtuins, a family of seven proteins that regulate the efficiency of cell function and promote health. Sirtuins are known to play a key role in aging. SIRT6, nicknamed the longevity gene, is specifically responsible for organizing proteins and recruiting enzymes that repair DNA double-strand breaks. Interestingly, research has demonstrated that mice without SIRT6 age prematurely while mice with extra copies of SIRT6 live longer, leading to the hypothesis that species with stronger SIRT6 have more efficient DNA repair and, thus, live longer. The study carried out by the University of Rochester set out to confirm this hypothesis and determine if higher SIRT6 activity is present in longer-lived species.
Testing the Hypothesis
Step One: Researchers began by examining DNA repair in 18 species of rodents with lifespans ranging from 3 years for mice to 32 years for naked mole rats and beavers. It was found that rodents with longer lifespans, such as beavers, also had more efficient DNA repair due to more active and stronger SIRT6 genes. Thus, not only can SIRT6 vary in different species, it was determined that, in longer-lived species, it has evolved and become more efficient and stronger. “The SIRT6 protein seems to be the dominant determinant of lifespan. We show that at the cell level, the DNA repair works better, and at the organism level, there is an extended lifespan,” says Dirk Bohmann, PhD, professor of biomedical genetics at the University of Rochester and one of the three co-authors of the study. It was, thus, concluded that more efficient DNA double-strand break repair coevolves with longevity.
Step Two: Researchers then analyzed the molecular differences between the weaker SIRT6 genes found in mice and the stronger SIRT6 genes found in beavers. Five amino acids were identified in beaver SIRT6 that were responsible for DNA repair and enzyme functions. Beaver and mouse SIRT6 were then inserted into human cells. It was found that beaver SIRT6, compared to mouse SIRT6, was better at reducing stress-induced DNA damage in human cells. The same experiment was done on fruit flies. The lifespan of fruit flies increased more with beaver SIRT6 than with mouse SIRT6. The team concluded that organisms with longer lifespans have more active and potent SIRT6.
Taking research one step further
Humans have a longer lifespan than both mice and beavers. There are, however, species that live longer than humans, such as the bowhead whale, which can live more than 200 years. Researchers now want to analyze whether these species have stronger SIRT6 genes than humans to understand if the whale’s genes have evolved to become more efficient. If this is proved true, this research may lead to new ways to improve the strength of human SIRT6 genes and, thus, increase DSB repair. Defects in DNA repair cause a number of diseases that affect a wide variety of body systems. Improving and increasing DSB repair may be just the answer to preventing diverse age-related diseases. “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,” says Vera Gorbunova, professor of biology at the University of Rochester and co-author of the study.
Mutations and damage in an organism’s DNA are a natural part of life that can be corrected by DNA repair. Impaired DNA repair can lead to shortened life span, rapid aging and a variety of diseases, including cancer. Understanding the role of SIRT6 in DNA double-strand break repair and the function and potency of SIRT6 in different species with different life spans has many positive implications for regulating DNA repair in the future. Scientists may find new ways to improve the activity and potency of our own SIRT6 genes or they may add additional SIRT6 genes to our cells to improve DSB repair. Future manipulation of the DNA-repair protein SIRT6 could be essential in creating more enhanced therapeutic responses to age-associated conditions and diseases.
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