間接證據(jù)表明,，在衰老過(guò)程中造血干細(xì)胞和前體細(xì)胞功能衰退受來(lái)自微環(huán)境或干細(xì)胞小環(huán)境的信號(hào)的影響，但一直沒有支持這一假設(shè)的實(shí)驗(yàn)證據(jù)?，F(xiàn)在,，用小鼠所做的一項(xiàng)研究證實(shí)，干細(xì)胞支撐環(huán)境中的細(xì)胞所發(fā)生的與年齡相關(guān)的變化的確能夠引起造血干細(xì)胞喪失功能,。
小環(huán)境細(xì)胞跟年齡相關(guān)的缺陷,，是通過(guò)暴露于一個(gè)年輕的循環(huán)系統(tǒng)、或通過(guò)對(duì)保守型長(zhǎng)壽調(diào)控因子的中和來(lái)系統(tǒng)性地調(diào)控和逆轉(zhuǎn)的,，該保守型長(zhǎng)壽調(diào)控因子即骨髓微環(huán)境中的“胰島素樣生長(zhǎng)因子-1”（IGF-1）,。所以，衰老動(dòng)物血液中的相關(guān)因子是通過(guò)局部小環(huán)境細(xì)胞來(lái)誘導(dǎo)干細(xì)胞與年齡相關(guān)的破壞的,。這表明,，以循環(huán)環(huán)境為目標(biāo)來(lái)維持小環(huán)境細(xì)胞和干細(xì)胞的功能，也許可以延長(zhǎng)老化血液系統(tǒng)的年輕功能,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 463, 495-500 (28 January 2010) | doi:10.1038/nature08749
Systemic signals regulate ageing and rejuvenation of blood stem cell niches
Shane R. Mayack1, Jennifer L. Shadrach1, Francis S. Kim1 & Amy J. Wagers1
1 Department of Stem Cell and Regenerative Biology, Harvard University, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02115, USA
2 Correspondence to: Amy J. Wagers1 Correspondence and requests for materials should be addressed to A.J.W.
Ageing in multicellular organisms typically involves a progressive decline in cell replacement and repair processes, resulting in several physiological deficiencies, including inefficient muscle repair, reduced bone mass, and dysregulation of blood formation (haematopoiesis). Although defects in tissue-resident stem cells clearly contribute to these phenotypes, it is unclear to what extent they reflect stem cell intrinsic alterations or age-related changes in the stem cell supportive microenvironment, or niche. Here, using complementary in vivo and in vitro heterochronic models, we show that age-associated changes in stem cell supportive niche cells deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction. Furthermore, we find that age-dependent defects in niche cells are systemically regulated and can be reversed by exposure to a young circulation or by neutralization of the conserved longevity regulator, insulin-like growth factor-1, in the marrow microenvironment. Together, these results show a new and critical role for local and systemic factors in signalling age-related haematopoietic decline, and highlight a new model in which blood-borne factors in aged animals act through local niche cells to induce age-dependent disruption of stem cell function.
