Specific prediction of mortality by oxidative stress-induced damage to RNA vs. DNA in humans.
Anders JorgensenIvan BrandslundChristina EllervikTrine HenriksenAllan WeimannPer Kragh AndersenHenrik E PoulsenPublished in: Aging cell (2023)
Modifications of nucleic acids (DNA and RNA) from oxidative stress is a potential driver of aging per se and of mortality in age-associated medical disorders such as type 2 diabetes (T2D). In a human cohort, we found a strong prediction of all-cause mortality by a marker of systemic oxidation of RNA in patients with T2D (n = 2672) and in nondiabetic control subjects (n = 4079). The finding persisted after the adjustment of established modifiers of oxidative stress (including BMI, smoking, and glycated hemoglobin). In contrast, systemic levels of DNA damage from oxidation, which traditionally has been causally linked to both T2D and aging, failed to predict mortality. Strikingly, these findings were subsequently replicated in an independent general population study (n = 3649). The data demonstrate a specific importance of RNA damage from oxidation in T2D and general aging.
Keyphrases
- oxidative stress
- dna damage
- nucleic acid
- type diabetes
- cardiovascular events
- hydrogen peroxide
- diabetic rats
- ischemia reperfusion injury
- single molecule
- magnetic resonance
- healthcare
- induced apoptosis
- circulating tumor
- cell free
- body mass index
- cardiovascular disease
- smoking cessation
- magnetic resonance imaging
- nitric oxide
- physical activity
- skeletal muscle
- electronic health record