Scientists at the University of California, Berkeley, have identified a new molecular pathway critical to aging, and confirmed that the process can be manipulated to help make old blood like new again.  The researchers found that blood stem cells’ ability to repair damage caused by inappropriate protein folding in the mitochondria, a cell’s energy station, is critical to their survival and regenerative capacity.  The discovery, published in the journal Science, has implications for research on reversing the signs of aging, a process thought to be caused by increased cellular stress and damage.

Ultimately, a cell dies when it can’t deal well with stress the team explain.  They found that by slowing down the activity of mitochondria in the blood stem cells of mice, they were able to enhance their capacity to handle stress and rejuvenate old blood. This confirms the significance of this pathway in the aging process.

Mitochondria host a multitude of proteins that need to be folded properly to function correctly. When the folding goes awry, the mitochondrial unfolded-protein response, or UPRmt, kicks in to boost the production of specific proteins to fix or remove the misfolded protein.

The researchers identified the importance of UPRmt in blood stem cell aging while studying a class of proteins known as sirtuins, which are increasingly recognized as stress-resistance regulators.  The team noticed that levels of one particular sirtuin, SIRT7, increase as a way to help cells cope with stress from misfolded proteins in the mitochondria. Notably, SIRT7 levels decline with age.

The team note that adult stem cells are normally in a quiescent, standby mode with little mitochondrial activity. They are activated only when needed to replenish tissue, at which time mitochondrial activity increases and stem cells proliferate and differentiate. When protein-folding problems occur, however, this fast growth could lead to more harm.

The team isolated blood stem cells from aged mice and found that when they increased the levels of SIRT7, the researchers were able to reduce mitochondrial protein-folding stress.  They then transplanted the blood stem cells back into mice, and SIRT7 improved the blood stem cells’ regenerative capacity.

The current study found that blood stem cells deficient in SIRT7 proliferate more. The team state that the faster growth is due to increased protein production and increased activity of the mitochondria, and slowing things down appears to be a critical step in giving cells time to recover from stress.

The team surmise that until this study, it was unclear which stress signals regulated the transition of stem cells to and from the quiescent mode, and how that related to tissue regeneration during aging; by identifying the role of this mitochondrial pathway in blood stem cells they have provided the medical community with a new target for controlling the aging process.

Source:  University of California, Berkeley