accumulation of long-chain glycosphingolipids during aging is prevented by caloric restriction长链积累鞘糖脂在老化是阻止通过热量限制.pdfVIP

Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction ´ ´ ´ 1 2 2 2 Marıa Jose Hernandez-Corbacho , Russell W. Jenkins , Christopher J. Clarke , Yusuf A. Hannun , Lina M. Obeid1,3, Ashley J. Snider1,3, Leah J. Siskind1,3* 1 Department of Medicine Medical University of South Carolina, Charleston, South Carolina, United States of America, 2 Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America, 3 Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, United States of America Abstract Background: Chronic kidney disease and end-stage renal disease are major causes of morbidity and mortality that are seen far more commonly in the aged population. Interestingly, kidney function declines during aging even in the absence of underlying renal disease. Declining renal function has been associated with age-related cellular damage and dysfunction with reports of increased levels of apoptosis, necrosis, and inflammation in the aged kidney. Bioactive sphingolipids have been shown to regulate these same cellular processes, and have also been suggested to play a role in aging and cellular senescence. Methodology/Principal Findings: We hypothesized that alterations in kidney sphingolipids play a role in the declining kidney function that occurs during aging. To begin to address this, the sphingolipid profile was measured in young (3 mo), middle aged (9 mo) and old (17 mo) C57BL/6 male mice. Interestingly, while modest changes in ceramides and sphingoid bases were evident in kidneys from older mice, the most dramatic elevations were seen in long-chain hexosylceramides (HexCer)