Deep learning reveals diverging effects of altitude on aging

Abstract

Aging is influenced by a complex interplay of multifarious factors, including an individuals genetics, environment, and lifestyle. Notably, high altitude may impact aging and age-related diseases through exposures such as hypoxia and ultraviolet radiation. To investigate this, we mined summary exposure value as a measure of risk exposure levels, and disability-adjusted life years (DALYs) as a measure of disease burden from the Global Health Data Exchange (GHDx) for each subnational region of Ethiopia, a country with considerable differences in the living altitude. We conducted a cross-sectional clinical trial involving 227 highland and 202 lowland dwellers from the Tigray region in Northern Ethiopia to gain a general insight into the biological aging at high altitudes. Notably, we observed significantly lower risk exposure rates and a reduced disease burden in higher-altitude regions of Ethiopia. When assessing biological aging using facial photographs, we found a faster rate of aging with increasing elevation, likely due to greater UV exposure. Conversely, analysis of nuclear morphologies of peripheral blood mononuclear cells in blood smears (PBMCs) with five different senescence predictors revealed a significant decrease in DNA damage-induced senescence in both monocytes and lymphocytes with increasing elevation. Overall, our findings suggest that disease and DNA damage-induced senescence decreases with altitude increase in agreement with the idea that chronic hypoxic stress may drive aging.