The Role of the Microenvironmental Niche in Declining Stem-Cell Functions Associated with Biological Aging - PubMed (original) (raw)

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The Role of the Microenvironmental Niche in Declining Stem-Cell Functions Associated with Biological Aging

Nathan A DeCarolis et al. Cold Spring Harb Perspect Med. 2015.

Abstract

Aging is strongly correlated with decreases in neurogenesis, the process by which neural stem and progenitor cells proliferate and differentiate into new neurons. In addition to stem-cell-intrinsic factors that change within the aging stem-cell pool, recent evidence emphasizes new roles for systemic and microenvironmental factors in modulating the neurogenic niche. This article focuses on new insights gained through the use of heterochronic parabiosis models, in which an old mouse and a young circulatory system are joined. By studying the brains of both young and old mice, researchers are beginning to uncover circulating proneurogenic "youthful" factors and "aging" factors that decrease stem-cell activity and neurogenesis. Ultimately, the identification of factors that influence stem-cell aging may lead to strategies that slow or even reverse age-related decreases in neural-stem-cell (NSC) function and neurogenesis.

Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

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Figures

Figure 1.

Figure 1.

Hypothesized aging effects on neural stem cells. (A) In the young brain, neural stem cells (green) have low amounts of DNA damage but high amounts of telomerase activity. Astrocytes (purple) provide trophic support and circulating “youthful” factors from the blood (red) support a neurogenic environment, in which neural stem cells divide into neuroblasts (blue), which mature into neurons (magenta). (B) In contrast, in the aging brain, neural stem cells accumulate DNA damage and show decreased telomerase activity. Further, astrocytes provide less trophic support and “aging” factors increase in concentration in blood. In the aging brain, therefore, fewer neuroblasts are produced and neurogenesis is decreased; on the other hand, more astrocytes are produced. FGF, Fibroblast growth factor; VEGF, vascular endothelial growth factor.

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