The Crucial Roles of Phospholipids in Aging and Lifespan Regulation

Abstract

Phospholipids are major membrane lipids that consist of lipid bilayers. This basic cellular structure acts as a barrier to protect the cell against various environmental insults and more importantly, enables multiple cellular processes to occur in subcellular compartments. Numerous studies have linked the complexity of membrane lipids to signal transductions, organelle functions, as well as physiological processes, and human diseases. Recently, crucial roles for membrane lipids in the aging process are beginning to emerge. In this study, we summarized current advances in our understanding of the relationship between membrane lipids and aging with an emphasis on phospholipid species. We surveyed how major phospholipid species change with age in different organisms and tissues, and some common patterns of membrane lipid change during aging were proposed. Further, the functions of different phospholipid molecules in regulating healthspan and lifespan, as well as their potential mechanisms of action, were also discussed.

Phosphatidylethanolamine N-Methyltransferase Knockout Modulates Metabolic Changes in Aging Mice

“…Newly emerging data are indicating that the biosynthesis of phospholipids (PLs), triglycerides, fatty acids, and sphingolipids plays a key role in lifespan regulation [ 13 , 14 , 15 ]. Notably, PLs are the major components of membranes in eukaryotic cells [ 16 , 17 ], and their association with aging has been demonstrated recently [ 18 ]. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the two most abundant PLs in mammalian cells and are important building blocks for more complex PLs [ 14 , 19 , 20 ].…”

“…It is unclear whether the methylation of PE by PEMT regulates the progression of aging because the levels of both substrate and product, i.e., PE and PC, are found to either increase or decrease in various aged tissues from humans, mice, or nematodes [ 18 ]. Interestingly, the dietary supplementation of both PE and PC has been found to contribute to lifespan extension in C. elegans through the same mechanism that reduces insulin/IGF-1-like signaling and promotes DAF-16 activity [ 44 , 45 , 46 ].…”

Phosphatidylethanolamine N-methyltransferase Knockout Modulates Metabolic Changes in Aging Mice

“…An emerging body of data indicates that biosynthesis of phospholipids (PLs), triglycerides, fatty acids, and sphingolipids plays a key role in lifespan regulation [13][14][15]. Notably, PLs are the major components of membranes in eukaryotic cells [16,17], and their association to aging has been demonstrated recently [18]. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the two most abundant PLs in mammalian cells and are important building blocks for more complex PLs [14,19,20].…”

“…It is unclear whether methylation of PE by PEMT regulates the progression of aging because the levels of both substrate and product, i.e. PE and PC, are found to either increase or decrease in various aged tissues from human, mouse, or nematodes [18]. Interestingly, dietary supplementation of both PE and PC has been found to contribute to lifespan extension in C. elegans through the same mechanism that reduces insulin/IGF-1like signaling and promotes DAF-16 activity [44][45][46].…”

“…Interestingly, dietary supplementation of both PE and PC has been found to contribute to lifespan extension in C. elegans through the same mechanism that reduces insulin/IGF-1like signaling and promotes DAF-16 activity [44][45][46]. Several unsaturated PCs play a protective role against neurodegenerative diseases in humans [18]. A decrease in PE levels with aging has been observed in C. elegans and mice [47,48], whereas an increase in PE levels prolonged lifespan in yeast and flies and increased the replicative viability of mam-malian cells [49].…”