Damage to nuclear DNA occurs constantly, and near all of it is immediately repaired. A tiny fraction lingers, however, and over time a burden of mutational damage builds up in tissues throughout the body. It is an open question as to how large a component of degenerative aging is a direct result of this damage, under normal circumstances. High rates of mutation in individuals with disabled DNA repair mechanisms shorten life span and accelerate the onset of age-related conditions, sometimes dramatically, but that doesn't necessarily mean the DNA damage is important in aging at levels exhibited in normal individuals. The best approach to firm data is to find a way to suppress or repair mutations without affecting other mechanisms, but the life-extending interventions that are known to slow the accumulation of DNA damage also have many other beneficial effects on metabolism. As reported here, for example, calorie restriction slows the pace at which the burden of DNA damage grows over time. Calorie restriction also improves cell function and health in numerous other ways, however, producing sweeping changes in the operation of cells and systems throughout the body that are unrelated to DNA damage.
Past studies in animals have shown that a large reduction in the number of calories they consume, called caloric restriction, extends their lifespans and slows aspects of aging. But whether caloric restriction also slows the rate at which mutations occur with age had not been investigated across the genome, the complete set of genetic material present in every cell. A new study has shown that caloric restriction reduced the level of mutations across several tissues in mice that were fed 30 percent fewer calories than they would have ingested if allowed to eat freely.
The study analyzed the effect of caloric restriction on different types of genetic changes. They found that to varying degrees across tissues, it dialed down the level of substitution mutations, in which one DNA letter is swapped for another, and insertion and deletion mutations, in which one or more DNA letters are added to or missing from the genome. The study results also showed that the impact of caloric restriction varies across tissues and cell types, as well as across the genome. For example, liver cells showed a greater reduction in mutation burdens with caloric restriction than kidney or brain cells.
Surprisingly, in liver and kidney cells, the reduction in the number of mutations from caloric restriction was greatest in the least-active regions of the genome, which contain either no genes or genes not being used by a given cell. One possible explanation is that if caloric restriction reduces DNA damage across the genome, active regions of the genome would not benefit as much because those regions already repair DNA damage frequently.
Link: https://nyulangone.org/news/feeding-mice-fewer-calories-reduces-dna-mutations
View the full article at FightAging
