Aging Cell Review Introduces Oxygenaging, a Framework for Studying Aging as a Disruption of the Oxygen Pathway from the Lungs to the Mitochondria
Aging Cell Review Introduces Oxygenaging, a Framework for Studying Aging as a Disruption of the Oxygen Pathway from the Lungs to the Mitochondria
On August 28, the authors of a review published in Aging Cell described Oxygenaging as a physiological framework for aging. They link age-related changes in the lungs, blood vessels, and cells to how precisely the body matches oxygen delivery to energy use in tissues.
After inhalation, oxygen passes from the lungs into the blood, binds to hemoglobin, travels through the heart and blood vessels, leaves the capillaries, enters the tissues, and reaches the mitochondria, the cellular structures that extract energy from nutrients. The authors call this sequence the oxygen cascade.
Aging can alter gas exchange in the lungs, the heart's capacity to increase blood output, and the function of the microcirculation, the network of the smallest blood vessels that distributes blood within tissues. Blood oxygen saturation therefore describes only one part of the pathway. A cell receives enough oxygen only when blood flow and diffusion from the capillary to the cell match its energy requirements.
“The central idea of Oxygenaging is that the body depends on its ability to continually match oxygen delivery to tissue demand, rather than on oxygen availability alone.”
When oxygen levels fall, HIF, a family of proteins that changes gene activity, becomes active. This response can promote vascular support, increase the production of erythrocytes, the blood cells that carry oxygen, and alter energy use. The authors propose treating age-related failures of oxygen delivery and cellular adaptation as connected processes. A disruption at one stage of the cascade changes the conditions under which the next stage operates.
In a mouse model of a rare mitochondrial disease, air containing 11% oxygen nearly tripled the lifespan of animals with an HTRA2 mutation. The mutation impaired the removal of damaged proteins from mitochondria, which reduced the cells' ability to extract energy. The authors proposed that the lower oxygen level was better matched to the mitochondria's reduced capacity to use oxygen. This specific case shows why an oxygen regimen must be assessed in relation to how a particular tissue uses oxygen.
The authors also distinguish among different ways of modifying oxygen exposure. Intermittent hypoxia, which consists of brief, controlled episodes of reduced oxygen, tests neural and vascular plasticity. Hyperbaric oxygen temporarily increases the amount of oxygen dissolved in plasma. The authors associate alternating periods of reduced and elevated oxygen with mitochondrial quality control.
Oxygenaging provides a framework for identifying where oxygen delivery and energy use become mismatched in each tissue, then testing the mechanism responsible for the mismatch and finding a measure that can detect it.