8-OHdG (8-hydroxy-2'-deoxyguanosine)

8-OHdG (8-hydroxy-2'-deoxyguanosine) is an oxidatively modified nucleoside formed when reactive oxygen species (ROS) attack the C8 position of guanine in DNA; it is among the most abundant and best-characterized oxidative DNA lesions in nuclear and mitochondrial DNA. When OGG1 (8-oxoguanine DNA glycosylase-1) excises the damaged base, the nucleoside is released into circulation and excreted in urine, making urinary 8-OHdG — normalized to creatinine — a non-invasive readout of oxidative DNA damage and repair activity. Levels rise with age, are elevated in smokers, obese individuals, and those exposed to ionizing radiation or pollutants, and are consistently higher in patients with cancer, atherosclerosis, type 2 diabetes, and neurodegenerative disease than in healthy controls (Wu et al., 2004). These associations are observational; 8-OHdG reflects oxidative burden but has not been established as a causal driver of disease in humans, and antioxidant interventions that lower 8-OHdG have not demonstrated proven clinical benefit. Measurement is most reliable by LC-MS/MS or HPLC-ECD; commercial ELISA kits show cross-reactivity artifacts that can substantially inflate values relative to chromatographic methods, with discrepancies varying across kits and sample matrices (Korkmaz et al., 2018; Hu et al., 2004). In prospective cohort research, urinary 8-OHdG correlates only weakly with chronological age and does not reliably distinguish accelerated from normal biological aging, limiting its standalone utility as a longevity biomarker (Mukli et al., 2022).