More SIRT7 Improves Aged Stem Cell Regenerative Capacity

There is relatively little study of sirtuin 7 (SIRT7) in comparison to the better known and greatly overhyped sirtuin 1 (SIRT1). All members of the sirtuin family have broad influence over a range of fundamental cellular processes, and thus cataloging their roles in metabolism is an enormous undertaking, still in the early stages despite the mountains of data and years of work to date. Still, inroads are being made, but it remains to be seen whether they are any more likely to result in practical applications than the past decade of work on SIRT1.

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. Researchers stumbled upon 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 researchers 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. There has been little research on the UPRmt pathway, but studies in roundworms suggest that its activity increases when there is a burst of mitochondrial growth.

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. "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."

The new study found that blood stem cells deficient in SIRT7 proliferate more. This 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 researchers found. "When there's a mitochondrial protein-folding problem, there is a traffic jam in the mitochondria. If you prevent more proteins from being created and added to the mitochondria, you are helping to reduce the jam." Until this study, it was unclear which stress signals regulate the transition of stem cells to and from the quiescent mode, and how that related to tissue regeneration during aging. "Identifying the role of this mitochondrial pathway in blood stem cells gives us a new target for controlling the aging process."

Link: https://newscenter.berkeley.edu/2015/03/19/aging-research-finds-taking-it-slow-helps-cope-with-stress/

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