DNA Repair

Why DNA repair matters for longevity

Your DNA suffers damage tens of thousands of times per day. UV radiation, environmental chemicals, and metabolic byproducts constantly assault your genetic code. Without efficient repair mechanisms, this damage accumulates, leading to mutations, cellular dysfunction, and eventually cancer or accelerated aging ^[1]. Research has established that DNA damage causally contributes to aging and age-related diseases ^[2].

The connection between DNA repair and longevity is direct. People with inherited defects in DNA repair genes often develop premature aging syndromes. Studies on long-lived animals like naked mole-rats reveal they possess enhanced DNA repair capacity that helps them live up to 30 years, remarkable for a rodent of their size ^[3]. Conversely, accumulating evidence suggests that loss of genomic maintenance contributes to normal aging ^[4].

Major DNA repair pathways

Your cells deploy several specialized repair systems depending on the type of damage. Base excision repair handles small lesions like oxidized bases caused by oxidative stress, fixing about 20,000 such lesions daily ^[5]. Nucleotide excision repair removes bulky lesions including UV-induced thymine dimers, while mismatch repair corrects replication errors that escape proofreading ^[6].

Double-strand breaks pose the greatest threat to genome stability. These severe lesions trigger two main repair pathways: homologous recombination, which uses an undamaged sister chromosome as a template for precise repair, and non-homologous end joining, which rapidly fuses broken ends but can be error-prone ^[7]. Double-strand breaks become more frequent with age and defects in their repair accelerate aging ^[8].

How DNA repair declines with age

DNA repair capacity decreases as you get older. This decline stems from reduced expression of repair enzymes, decreased NAD+ levels needed for repair processes, and accumulated cellular stress. Research shows that repair efficiency drops significantly in aging cells, leading to mutation accumulation and genomic instability ^[9].

The consequences extend beyond cancer risk. Mitochondrial DNA repair mechanisms also deteriorate with age, contributing to mitochondrial dysfunction and reduced cellular energy production ^[10]. This creates a vicious cycle: impaired repair leads to more damage, which further reduces repair capacity. Understanding these mechanisms has led to interventions targeting DNA repair enhancement as a longevity strategy.

Supporting your DNA repair systems

Several evidence-based approaches can support DNA repair function. Regular exercise upregulates DNA repair enzyme expression and reduces oxidative stress. Adequate intake of nutrients like zinc, magnesium, and B vitamins provides cofactors required for repair enzymes ^[11]. NAD+ precursors such as NMN and NR may enhance repair capacity by fueling enzymes like PARPs that consume NAD+ to fix DNA damage ^[12].

Caloric restriction and intermittent fasting activate cellular stress responses that enhance DNA repair and maintenance pathways. These interventions reduce oxidative damage while upregulating repair mechanisms through sirtuin activation ^[13]. Sleep quality matters too, as DNA repair processes peak during deep sleep when cellular energy can be directed toward maintenance rather than activity.