老化：血液告訴老細胞表現出年輕的樣子
Blood tells old cells to act young
By Eric Bender, January 27, 2010
“These findings open up exciting new avenues of research, including the potential for studying other types of tissues that aren’t as well understood, in which aging may be regulated by stem-niche cell interactions in a similar way,” said lead first author Shane Mayack. “Over time, these findings may also influence the way blood disorders are treated,” the postdoc said. File photo by B. D. Colen/Harvard Staff
(PhysOrg.com) -- Harvard Stem Cell Institute (HSCI) researchers at the Joslin Diabetes Center (JDC) have taken a major step toward eventually understanding -- and perhaps slowing -- the aging process.
在 Joslin Diabetes Center (JDC) 的 Harvard Stem Cell Institute (HSCI) 研究者在朝向最終瞭解 -- 或許還能延緩 -- 老化過程上跨出重要的一步。
In a series of careful experiments, Amy J. Wagers and colleagues have demonstrated that the stem cells of old mice exposed to certain factors present in blood from young mice begin to act like young stem cells, with the process driven by signals from another type of cell nearby in the bone. In fact, not only do the blood stem cells begin to take on characteristics of younger cells, but the tissues of old mice exposed to this yet-to-be-identified factor or factors appear to be much more “youthful.
在一系列謹慎的實驗中， Amy J. Wagers 等人證明，年老老鼠的幹細胞暴露在年輕老鼠血液中的某些因子裡，會開始像年輕幹細胞般表現，而此過程由來自骨骼附近另一類型細胞的訊號所驅使。事實上，並非只有血液幹細胞開始呈現出較年輕細胞的特徵，還包括那些來自年老老鼠的組織。它們不是暴露在尚待確認的因子，就是暴露在那些顯然更加「年輕」的因子中。
This latest work by Wagers’ group is published in today’s edition of Nature. It advances the understanding of aging of the blood-forming "hematopoietic" system and points toward ways to treat age-related ailments via the blood.
Wagers 小組的最新研究發表在今日的 Nature 上。它促進造血（hematopoietic）系統老化的理解並指出經由血液治療老化相關疾病的方法。
Doug Melton, co-director of HSCI and co-chair of Harvard’s Department of Stem Cell and Regenerative Biology called the finds “important,” explaining that “the paper shows that cells and their ‘homes,’ known as the niche, both deteriorate with age. While that may not be a surprise, what is a source of amazement is the demonstration that young animals, through the action of insulin-like growth factor 1(IGF-1), can turn back the clock and rejuvenate aged blood cells.”
Doug Melton，HSCI 副所長以及哈佛幹細胞與再生生物學系副系主任（co-chair）稱此發現「重要」並解釋 "這篇論文證明，細胞以及它們的「家」，稱為利基（niche），一同隨著年齡退化。那也許不讓人感到意外，讓人驚異之處在於這個證明：「年輕動物，透過胰島素般的生長因子1的（IGF-1）作用，能使時鐘倒轉並使老化的血液細胞變年輕」。"
Previous work by other labs gave evidence that the decline in blood stem cell function that comes with age is partly intrinsic to the cells themselves. However, these cells also are affected by signals from other cells in the local bone marrow microenvironment or “niche.” An earlier study led by Shane Mayack, a postdoctoral fellow in Wagers’ lab, pinpointed bone-forming cells known as osteoblasts as key players in this signaling from the niche, and showed that osteoblasts play a particular role in blood stem cell maintenance and regeneration.
由其他實驗室所完成的先前研究提出證據指出，伴隨衰老而來的血液幹細胞功能衰退為細胞自身的部份本質。然而，這些細胞也受到某些訊號的影響。這些訊號來自於局部（local）骨髓微環境（或利基）的其他細胞。由 Shane Mayack（Wagers 實驗室的博士後研究）所領導的早期研究指出，在此利基的發訊（signaling）中，成骨細胞（osteoblasts）為關鍵角色，並證明成骨細胞在血液幹細胞維持與再生上扮演著特殊的角色。
For the latest paper, Mayack and her colleagues studied the blood stem cell aging process in young and old mice. The researchers found that as osteoblasts age, they change the signals that they send to stem cells, and that this change makes those cells less able to produce the right mixture of blood cells.
為了這篇最新的論文，Mayack 與她的同僚以年輕與年老老鼠研究血液幹細胞的老化過程。研究者們發現，當成骨細胞老化，它們改變送往幹細胞的訊號，而這種改變使這些細胞較無法產生血液細胞的正確混合。
More dramatically, in a series of tests in which two mice shared a common blood circulation, the scientists revealed that this aging mechanism could be reversed. In old mice paired with young mice, the existing populations of osteoblasts showed signs of rejuvenation. Remarkably, this rejuvenation was communicated to the stem cells as well, such that the blood-forming abilities of these aged mice took on much more “youthful” characteristics.
更引人注目地，在一系列試驗中（其中二隻老鼠共享相同的血液循環）科學家揭露，這種老化機制能被逆轉。在年老老鼠與年輕老鼠的搭配中，現存的成骨細胞族群展現出再生的訊號。很明顯地，回春也傳達至幹細胞，這些老化老鼠的造血能力展現出更多「年輕的」特徵。
“What’s most exciting is that the changes that occur in blood stem cells during aging are reversible, through signals carried by the blood itself,” said Wagers, an associate professor in Harvard’s Department of Stem Cell and Regenerative Biology, HSCI Principal Faculty member, and an investigator at the Joslin. “This means that the blood system offers a potential therapeutic avenue for age-related stem cell dysfunction.”
"最讓人驚訝的是，老化期間發生在血液幹細胞中的改變，可藉由血液本身所攜帶的那些訊號逆轉，" Wagers 表示，哈佛幹細胞與再生生物學系的副教授、HSCI 首席教員成員，同時也是在 Joslin（糖尿病中心）的研究者。"這表示，對老化相關的幹細胞機能不良來說，血液系統提供一種潛在的治療途徑。"
“These findings open up exciting new avenues of research, including the potential for studying other types of tissues that aren’t as well understood, in which aging may be regulated by stem-niche cell interactions in a similar way,” said Mayack. “Over time, these findings may also influence the way blood disorders are treated.”
"這些發現開啟了新的研究道路，包括研究其他尚未完全瞭解之組織類型的可能性，在其中，老化也許以類似方式由幹細胞--利基細胞的交互作用所調控，" Mayack 說。"隨著時間過去，這些發現也許會影響血液失調的治療方法。"
As a next step, investigators will hone in on how signals sent to and from osteoblasts are altered as the cells age. The Joslin team has begun by examining the role of IGF-1, a protein that other studies have shown can aid in regenerating skeletal muscle. To their surprise, they found that they could partially correct aging defects in osteoblasts by suppressing IGF-1, rather than enhancing it. “This difference highlights the complexity of the controls that are involved in cell regeneration,” Wagers said.
下一步，研究者將研究進出成骨細胞的訊號如何隨著細胞老化而改變。這個 Joslin 團隊從檢查 IGF-1 的角色，其他研究已證明這種蛋白質能幫助骨骼肌的再生。讓他們驚訝的是，他們發現他們能藉由抑制 IGF-1 而非強化它，在成骨細胞中部份地矯正老化缺陷。"這種差異強調了那些涉及細胞再生之控制的複雜性，" Wagers 說。
While the work does not directly address diabetes mechanisms, Wagers, a Howard Hughes Medical Institute Early Career Scientist, noted that “there’s more and more evidence of an overlap in the regulatory pathways that are implicated in aging and in type 2 diabetes.”
雖然這項研究並未直接對付糖尿病機制，不過 Wagers（一位 Howard Hughes Medical Institute Early Career Scientist）提到 "在涉及老化與乙型糖尿病（type 2 diabetes）的調控路徑中，有愈來愈多的證據相重疊。"
More information: http://www.nature.com/nature/journal/v463/n7280/abs/nature08749.html
Provided by Harvard University (news : web)
※ 相關報導：
＊ Systemic signals regulate ageing and rejuvenation of blood stem cell niches
http://www.nature.com/nature/journal/v463/n7280/abs/nature08749.html
Shane R. Mayack, Jennifer L. Shadrach, Francis S. Kim &
Amy J. Wagers
Nature 463, 495-500 (28 January 2010)
doi: 10.1038/nature08749
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