期刊论文详细信息
Aging Cell
Rifampicin reduces advanced glycation end products and activates DAF‐16 to increase lifespan in Caenorhabditis elegans
Sandeep Golegaonkar3  Syed S. Tabrez2  Awadhesh Pandit2  Shalini Sethurathinam2  Mashanipalya G. Jagadeeshaprasad3  Sneha Bansode3  Srinivasa-Gopalan Sampathkumar1  Mahesh J. Kulkarni3 
[1] Laboratory of Chemical Glycobiology, National Institute of Immunology, New Delhi, India;Molecular Aging Laboratory, National Institute of Immunology, New Delhi, India;Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune, India
关键词: advanced glycation end products;    aging;    Caenorhabditis elegans;    DAF‐16;    glycation;    lifespan;    rifampicin;   
DOI  :  10.1111/acel.12327
来源: Wiley
PDF
【 摘 要 】

Summary

Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MSE, we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions.

【 授权许可】

CC BY   
© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

【 预 览 】
附件列表
Files Size Format View
RO202107150000326ZK.pdf 807KB PDF download
  文献评价指标  
  下载次数:2次 浏览次数:3次