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Title: Age-Related Diseases and Their Therapeutic Implications, “Cell Membrane Theory of Senescence,” the Function of Bioactive Lipids in Aging, and Aging-Related Diseases
Abstract: Polyunsaturated fatty acids (PUFAs) are the most significant lipids and a necessary component of the cell membrane. The release of PUFAs from the cell membrane that form precursors to both pro- and anti-inflammatory bioactive lipids that take part in a number of cellular processes is induced by the activation of phospholipase A2 (PLA2). Gamma-linolenic acid (GLA), dihomo-GLA (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are PUFAs. aenoic acid) are produced by the action of desaturases, whose activity decreases with age, from dietary linoleic acid (LA) and alpha-linolenic acid (ALA). Aged cells therefore lack GLA, DGLA, AA, AA, EPA, and DHA as well as their metabolites. Additionally, LA, ALA, AA, EPA, and DHA can obtained exclusively through diet, and a lack of them (fatty acids) may indicate malnutrition and a lack of a number of vitamins, minerals, and trace elements, some of which are also crucial co-factors for the proper function of desaturases. Many times, despite not having a nutrient deficiency in other nutrients, patients have low plasma and tissue levels of GLA, DGLA, AA, EPA, and DHA (as seen in patients with hypertension and type 2 diabetes mellitus). Consequently, it is reasonable to assume that The decreased activity of desaturases and elongases is the cause of the deficiencies of GLA, DGLA, AA, EPA, and DHA observed in these conditions. Through protein kinase A-dependent activation of the SIRT1-PGC1 complex, PUFAs activate SIRT1, which increases the rate of fatty acid oxidation and prevents the lipid dysregulation linked to aging. The activation of SIRT1 delays aging. SIRT6 is the most important SIRT for genomic stability and intermediary metabolism. Mice lacking SIRT6 exhibit shortened Activated oncogenes are associated with a long lifespan, defects in DNA repair, and a high incidence of cancer. In addition to its anti-inflammatory effects at the transcriptional level, SIRT6 overexpression extends the lifespan of mice by lowering LDL and triglyceride levels, improving glucose tolerance, and reducing mortality. SIRT6 and other SIRTs are influenced by PUFAs and their anti-inflammatory metabolites, which results in their effects on metabolism, inflammation, and genome maintenance. AA, EPA, DGLA, GLA, and Different SIRTs (SIRt1 SIRT2, SIRT3, SIRT4, SIRT5, SIRT6), PPAR-, PARP, p53, SREBP1, intracellular cAMP content, PKA activity, and peroxisome proliferator-activated receptor coactivator 1- (PGC1-) are activated or suppressed by DHA and prostaglandin E2 (PGE2), lipoxin A4 (LXA4), and This suggests that modifications in desaturases, COX-2, 5-, 12-, and 15-LOX (cyclo-oxygenase and) activities lead to changes in the metabolism of bioactive lipids. lipoxygenases, respectively) may play a significant part in determining cell age, the onset of a number of diseases linked to aging, the stability of the genome, and the activation of genes and oncogenes. Therefore, strategies to maintain the homeostasis of bioactive lipids (such as GLA, DGLA, AA, EPA, DHA, PGE2, and LXA4) may halt the aging process and any accompanying metabolic abnormalities.
Keywords: aging; unsaturated fatty acids; bioactive lipids; inflammation; cell membrane; sirtuins
Paper Quality: SCOPUS / Web of Science Level Research Paper
Subject: Biomolecules
Writer Experience: 20+ Years
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