2025年11月25日出版的《细胞—代谢》杂志发表了美国科学家的一项最新研究成果。来自南加州大学的Peter J. Mullen研究小组报道了小鼠衰老的代谢图谱。

该团队分析了5个不同年龄的雄性和雌性小鼠12个器官的代谢变化。小组还开发了器官特异性代谢衰老时钟，用于识别衰老的代谢驱动因素，包括α -酮戊二酸，之前在小鼠中被证明可以延长寿命。研究人员还对生物钟进行了调整，以发现谷丙酸是衰老的潜在驱动因素，并表明它是由人体细胞合成的。最后，该研究组证实了羟脯氨酸在人类胰腺中随着年龄的增长而减少，强调他们的方法揭示了跨物种的见解。这项研究揭示了衰老过程的基本见解，并确定了维持器官健康的新治疗靶点。

据悉，人类的寿命越来越长，与年龄相关的疾病也越来越多，其中许多与代谢失调有关，但在衰老过程中，多器官的代谢如何变化尚不清楚。回答这个问题可能会揭示新的衰老机制和治疗方法。

附：英文原文

Title: A metabolic atlas of mouse aging

Author: Steven E. Pilley, Dominik Awad, Djakim Latumalea, Connie New, Edgar Esparza, Shuo Wang, Xuanyi Shi, Li Zhang, Maximilian Unfried, Jasinda H. Lee, Ernst Schmid, Ipsita Mohanty, Jenna L.E. Blum, Shivaanishaa Raventhiran, Esther Wong, Preeti R. Iyengar, Racheal Mulondo, Sriraksha Bharadwaj Kashyap, Darius Moaddeli, Peter Sajjakulnukit, Damien Sutton, Harrison K.A. Wong, Yaqi Gao, George Wang, Aeowynn J. Coakley, Gilberto Garcia, Ryo Higuchi-Sanabria, Anja Karlstaedt, Timothy L. Frankel, Marina Pasca di Magliano, Whitaker Cohn, Sophia Liu, Bingfei Yu, Pieter C. Dorrestein, Ernest Fraenkel, Shawn M. Davidson, William B. Tu, Brian K. Kennedy, Costas A. Lyssiotis, Peter J. Mullen

Issue&Volume: 2025-11-25

Abstract: Humans are living longer and experiencing more age-related diseases, many of which involve metabolic dysregulation, but how metabolism changes in multiple organs during aging is not known. Answering this could reveal new mechanisms of aging and therapeutics. Here, we profile metabolic changes in 12 organs in male and female mice at 5 different ages. We also develop organ-specific metabolic aging clocks that identify metabolic drivers of aging, including alpha-ketoglutarate, previously shown to extend lifespan in mice. We also use the clocks to uncover that carglumic acid is a potential driver of aging and show that it is synthesized by human cells. Finally, we validate that hydroxyproline decreases with age in the human pancreas, emphasizing that our approach reveals insights across species. This study reveals fundamental insights into the aging process and identifies new therapeutic targets to maintain organ health.

DOI: 10.1016/j.cmet.2025.10.016

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00476-0