A groundbreaking study on aging has been published in the Journal of Clinical Investigation.
The scientists set out to understand how DNA damage and aging are related. It is believed damage to DNA from oxidation progressively accumulates leading cells to become senescent and the organism as a whole to age.
Normally cells have networking mechanisms that detect and repair DNA damage when it occurs.
A transcription factor called NF-κB is known to increase in concentration as organisms age. This factor is integral in mounting a repair response when cells are exposed to stress.
The researchers hypothesized that aging occurrs as a direct result of NF-κB activation. They reasoned that aging might be a by-product of the repair and that by inhibiting NF-κB aging might be reduced.
They developed two methods to inhibit NF-κB in mice. First they genetically removed one of the genes encoding a subunit of NF-κB. In the other method they used a pharmacologic inhibitor of NF-κB. This compound is an 11 unit peptide called NBD which is fused to a protein transduction domain. This agent was administered to mice three times per week beginning at 5 weeks of age.
It was found that inhibition of NF-κB “delayed the age-related symptoms and pathologies of progeroid mice,” and “reduced oxidative DNA damage and stress and delayed cellular senescence.”
They concluded “these results indicate that the mechanism by which DNA damage drives aging is due in part to NF-κB activation. IKK/NF-κB inhibitors are sufficient to attenuate this damage and could provide clinical benefit for degenerative changes associated with accelerated aging disorders and normal aging.”