New research has identified a chemical link that plays a vital role in the repair of cellular DNA, with researchers hoping that the new results can lead to a breakthrough in age-related health problems and cancers.
The chemical is nicotinamide adenine dinucleotide (NAD), a cellular signalling molecule that research has shown to have many crucial functions. Importantly, NAD aids in the production of ATP, the energy currency of cells, and it also serves in the maintenance of cellular homeostasis, energy metabolism and, as detailed in the present study, DNA repair.
DNA molecules are constantly under attack from a myriad of sources, not just in human beings but in all life forms, where the chemical bonds holding together the genetically encoded strands of DNA are broken or the structural integrity is altered by radiation, oxidation and the metabolic processes occurring within cells. This natural process is taken as a given, and so is our body’s ability to repair the molecular damage through a variety of mechanisms.
Yet as our body’s age, so do our cells’ ability to repair DNA, leading to many age-related health problems including the development of cancers. NAD plays a role in DNA repair, yet the concentration of NAD in our cells is known to decline with age, taking away some of the body’s ability to repair itself.
The new study comes from an international research team including members from Harvard Medical School, the University of Bayreuth in Germany, the University of New South Wales in Sydney, Australia, and the Department of Pharmacology, University of Alberta in Edmonton. Published in the journal Science, the study consists of two stages, one in which NAD’s ability to help in DNA repair was confirmed (using human embryonic kidney cells) and another in which the same process was observed in older mice.
The researchers found that NAD helped by binding to a certain protein (DBC1) which interferes with DNA repair processes and, further, that when the aging mice were given more of the chemical precursor to NAD so as to boost their NAD concentrations, the DBC1 protein was more often kept from affecting DNA repair, a key finding concerning the aging process.
“As mice age and NAD+ concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD+,” say the study’s authors. “Thus, NAD+ directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.”
The researchers see their work as currently in its initial stages, however, as there is still much to uncover about NAD, its function and why concentration levels decline with age. Yet, the results are a significant step, perhaps one day helping to slow down some of the cellular damage that occurs with aging, says senior author David Sinclair, professor in the Department of Genetics at HMS and professor at the University of New South Wales School of Medicine in Sydney, who says their results are “the closest we are to a safe and effective anti-ageing drug that’s perhaps only three to five years away from being on the market if the trials go well.”
“Our results unveil a key mechanism in cellular degeneration and aging, but beyond that they point to a therapeutic avenue to halt and reverse age-related and radiation-induced DNA damage,” says Sinclair to Phys.org.