- Reduced oxygen supply to tissues may be partly responsible for age-related physical and cognitive decline.
- A receptor in the membrane of red blood cells is known to promote the release of oxygen from hemoglobin at high altitudes.
- A new study in mice found that the same receptor mitigates the cognitive decline and hearing loss associated with aging by improving oxygen supply to tissues.
- The discovery provides potential targets for new anti-aging drugs.
Between 1960 and 2015, average life expectancy at birth increased by a decade in the United States, from 70 to 79 years of age, and is expected to rise still further.
While this reflects the success of modern medicine, it also means that an increasing proportion of the population has to live with the physical and cognitive deterioration that comes with old age.
Finding new ways to help people age well, and not just live longer, has become a priority.
One clue to achieving this lies in the idea that aging is accompanied by a decrease in the supply of oxygen to tissues. Researchers suggest that this triggers immune changes that promote chronic inflammation, which is linked to almost all conditions of old age.
Among the many potential consequences of this “inflammaging” could be cognitive decline and hearing loss.
There is, however, evidence that improving oxygen supply can reverse some cellular signs of aging. For example, one small study found that hyperbaric oxygen therapy, which is a treatment that involves breathing almost pure oxygen, appeared to rejuvenate immune cells in older adults.
Another study found that red blood cells respond to the low-oxygen conditions of high altitudes by increasing the amount of oxygen they deliver to tissues. They do this through increased signaling by a receptor in their membrane, known as the adenosine receptor A2B or ADORA2B, which promotes the release of oxygen by hemoglobin.
Aging in general, but particularly some neurodegenerative conditions such as Alzheimer’s disease, is associated with reduced activity in the same metabolic pathway.
Now, research in mice led by the University of Texas McGovern Medical School in Houston has found that ADORA2B also appears to stave off some of the effects of aging by increasing oxygen supply to tissues.
In theory, a drug that increases activity in this pathway could help combat age-related declines.
“So far, there is no such drug available,” Dr. Yang Xia, who led the study, told Medical News Today.
However, she also noted that the discovery that hyperbaric oxygen treatment can reverse some of the effects of aging on human blood cells suggests that it might work.
“Our finding immediately highlights that enhancing O2 [oxygen] delivery mediated by ADORA2B signaling is likely a new rejuvenating approach,” she said.
The research appears in the journal PLOS Biology.
The scientists studied mice genetically engineered to lack ADORA2B in the membranes of their red blood cells.
These animals appeared to age at a younger age than normal mice. They also experienced steeper declines in their spatial learning, memory, and hearing abilities.
On a cellular level, the rodents showed signs of inflammaging, including increased production of pro-inflammatory cytokines, or signaling molecules that encourage inflammation.
“Our findings reveal that the red blood cell ADORA2B signaling cascade combats early onset of age-related decline in cognition, memory and hearing by promoting oxygen delivery in mice and immediately highlight multiple new rejuvenating targets,” says Dr. Xia.
However, more research is needed to determine whether ADORA2B levels decline with age in normal mice, and whether drugs that activate the ADORA2B pathway can slow down age-related loss of hearing and cognition.
Studies in humans may also be on the cards.
“We plan to validate our mouse finding in humans in the near future,” Dr. Xia told MNT.
One of the limitations of studying aging by conducting experiments in animals such as mice and fruit flies is that their life spans are so much shorter than ours.
Humans are already evolutionarily adapted to live longer than these creatures, so the potential for any further gains in healthy life spans may be more limited.