一項對小鼠的研究發(fā)現(xiàn),,科學家終于有可能通過測量大腦的乳酸濃度從而監(jiān)測衰老的進程,。科學家長久以來懷疑,,線粒體DNA(mtDNA)的逐漸損壞導致了衰老,。線粒體DNA(mtDNA)是從食物中制造能量所需的遺傳物質(zhì)。此前的研究已經(jīng)把人類線粒體DNA(mtDNA)的突變與中樞神經(jīng)系統(tǒng)的衰老相關(guān)疾?。ㄈ绨⑵澓D『团两鹕,。┞?lián)系了起來,。Lars Olson及其同事調(diào)查了這種理論,方法是檢查了正常和過早衰老的小鼠的大腦的代謝過程,。
這組科學家發(fā)現(xiàn)線粒體DNA(mtDNA)機能障礙引發(fā)了小鼠大腦的一種代謝變化,,它可能改變控制乳酸形成的特定基因的表達。這組作者說,,這種變化導致了大腦乳酸濃度增加,,利用非侵入式成像技術(shù)可能探測到它。這組作者說,,這些發(fā)現(xiàn)還提示乳酸濃度的上升在其他衰老指標之前出現(xiàn),,而未來的研究可能使用乳酸濃度探測中樞神經(jīng)系統(tǒng)的與衰老有關(guān)的疾病。(生物谷Bioon.com)
生物谷推薦英文摘要:
PNAS doi: 10.1073/pnas.1008189107
High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio
Jaime M. Rossa,b,1, Johanna ?bergc, Stefan Brenéd, Giuseppe Coppotellie, Mügen Terziogluf, Karin Pernolda, Michel Goinyg, Rouslan Sitnikovh, Jan Kehrg, Aleksandra Trifunovici, Nils-G?ran Larssonf,j, Barry J. Hofferb, and Lars Olsona,1
At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate → lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes.