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A lipidome landscape of aging in mice

脂质体 单酰甘油脂肪酶 脂类学 糖脂 生物化学 鞘脂 生物 脂质代谢 神经酰胺 酰基转移酶 内大麻素系统 生物合成 细胞凋亡 受体
作者
Hiroshi Tsugawa,Tomoaki Ishihara,Kota Ogasa,Seigo Iwanami,Aya Hori,Mikiko Takahashi,Yutaka Yamada,Aki Minoda,Makoto Arita
出处
期刊:Research Square - Research Square 被引量:1
标识
DOI:10.21203/rs.3.rs-2139359/v1
摘要

Abstract Understanding the molecular mechanisms associated with aging is important to improve the longevity of healthy individuals. Herein, we performed untargeted lipidomics to elucidate the relationship between aging and lipid metabolism in 13 mouse tissues at various life stages (2, 12, 19, and 24 months), in which sex and microbiome dependencies (specific pathogen free/germ free) were investigated. By analyzing 2,817 unique molecular profile data of 121 lipid subclasses, we characterized the common and tissue-specific lipidome changes associated with aging. For example, bis(monoacylglycerol)phosphate containing polyunsaturated fatty acids was enriched in various organs during aging, while other phospholipids containing saturated and monounsaturated fatty acids were decreased. In addition, we discovered an age-dependent increase of sulfonolipid (SL), which is biosynthesized in Alistipes and Odoribacter genera. SL molecules were absent in germ-free mice. Furthermore, the molecules appeared to be translocated from the intestinal lumen to various tissues such as the liver, kidney, and spleen. In the kidney, the associations of glycolipids such as galactosyl ceramides (GalCer), galabinosyl ceramides (Gal2Cer), trihexosyl ceramides (Hex3Cer), and mono and digalactosyl diacylglycerols were found in male mice, in which two lipid classes Gal2Cer and Hex3Cer were significantly enriched in aged mice. Integrated analysis of the kidney transcriptome revealed uridine diphosphate galactosyltransferase UGT8a, alkylglycerone phosphate synthase, and fatty acyl-CoA reductase 1 as potential enzymes responsible for male-specific glycolipid biosynthesis in vivo, which would be relevant to sex dependency in kidney diseases. Our lipidome results will become an important resource, led to the understanding of the molecular mechanisms underlying cellular senescence and age-related diseases.
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