Reactive Oxygen Species and Stem Cell Decline

Here is a review with some interesting implications:

Hematopoietic stem cells (HSCs) are defined by their ability both to self-renew and to give rise to fresh blood cells throughout the lifetime of an animal. The failure of HSCs to self-renew during aging is believed to depend on several intrinsic (cell-autonomous) and extrinsic (non-cell-autonomous) factors. In this review, we focus on how dysregulation of reactive oxygen species (ROS) and disruptions of genomic stability can impair HSC functions.

Recently, it was shown that long-term self-renewing HSCs normally possess low levels of intracellular ROS. However, when intracellular ROS levels become excessive, they cause senescence or apoptosis, resulting in a failure of HSC self-renewal. Repression of intracellular ROS levels in HSCs by treatment with an antioxidant that scavenges ROS can rescue HSC functions, indicating that excess ROS levels are at the root of HSC failure.

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Further investigations on the molecular mechanisms of ROS regulation and on the manipulation of excess ROS levels could lead to the development of novel therapeutics for hematopoietic diseases, regenerative medicine, and the prevention of leukemia.

Rising levels of ROS with age are due to dysfunctional mitochondria. Could it be that the steady accumulation of mitochondrial damage - and the rising levels of ROS that result from that damage - contributes to shutting down stem cells in addition to all the other issues it causes?

Targeting antioxidants to stem cells in additional to cellular mitochondria begins to sound like something worth trying in mice. Will it extend healthy life by keeping stem cells active for longer, or will increased stem cell activity bring more and earlier cancer due to the other damage caused by mitochondrial ROS? If the root problem is the reactive oxygen species, tackling that problem first might be more effective than trying to keep cellular system running in the face of the ROS assault.

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