Mild mitochondrial stress experienced early in life can have beneficial effects on the life span of organisms through epigenetic regulations.
A research team led by Prof. TIAN Ye at Institute of Genetics and Developmental Biology of Chinese Academy of Sciences reported that acetyl–coenzyme A (CoA) represents a critical mitochondrial signal to regulate aging through the chromatin remodeling and histone deacetylase complex (NuRD) in Caenorhabditis elegans. Upon mitochondrial stress, the impaired tricarboxylic acid cycle results in a decreased level of citrate, which accounts for reduced production of acetyl-CoA and consequently induces nuclear accumulation of the NuRD and a homeodomain-containing transcription factor DVE-1, thereby enabling decreased histone acetylation and chromatin reorganization. The metabolic stress response is thus established during early life and propagated into adulthood to allow transcriptional regulation for life-span extension. Furthermore, adding nutrients to restore acetyl-CoA production is sufficient to counteract the chromatin changes and diminish the longevity upon mitochondrial stress. The findings of the study uncover the molecular mechanism of the metabolite-mediated epigenome for the regulation of organismal aging.
The study was published in Science Advances on July 31. PhD student ZHU Di at University of Chinese Academy of Sciences and associate researcher WU Xueying at Institute of Genetics and Developmental Biology of Chinese Academy of Sciences contributed equally to the study, Prof. TIAN is the corresponding author. Prof. TIAN is also a doctoral supervisor at University of Chinese Academy of Sciences.
