The journal Science has published the work of researchers at the University of California, Berkeley, , who recently identified a new molecular pathway critical to the aging process. Their work has implications in possibly reversing the signs of aging in human beings.
The scientists have found a way to manipulate the process to make old blood function like new. They also found that the stem cells of blood have the ability to repair damage caused by dysfunctional protein folding in the micochrondria, which can be described as a cell’s energy station, and that ability is necessary for their ability to survive and regenerate. Scientists believe the aging process is caused by cellular stress and damage.
The study’s senior author is Danica Chen, an assistant professor in the Department of Nutritional Sciences and Toxicology. She writes:
Ultimately, a cell dies when it can’t deal well with stress. We found that by slowing down the activity of mitochondria in the blood stem cells of mice, we were able to enhance their capacity to handle stress and rejuvenate old blood. This confirms the significance of this pathway in the aging process.
The mitochondria of the cell host a number of proteins that must be folded properly to function correctly. When the folding process malfunctions, the mitochondrial unfolded-protein response, or UPRmt, plays a role to boost the production of certain proteins and repair or remove the misfolded protein.
Chen’s laboratory inadvertently discovered the importance of UPRmt while they were investigating a class of proteins called situins, which are known to be stress-resistance regulators. One of the sirtuins, SIRT7, increases to help cells cope with stress caused by the misfolded proteins. It is known that SIRT7 levels decline with age.
Most of the time, adult stem cells are in an inactive, standby mode with minimal mitochondrial activity. The cells are activated only when it is time to replenish tissue; then the mitochondrial activity ramps up, and the stem cells proliferate and differentiate. But when protein-folding problems happen, this accelerated growth can cause harm.
We isolated blood stem cells from aged mice and found that when we increased the levels of SIRT7, we were able to reduce mitochondrial protein-folding stress. We then transplanted the blood stem cells back into mice, and SIRT7 improved the blood stem cells’ regenerative capacity.
Identifying the role of this mitochondrial pathway in blood stem cells gives us a new target for controlling the aging process.