Bioactive Lipids and the Cell Membrane in Aging

Researchers here discuss, in some detail, what is known of age-related changes in the levels of various lipid molecules in cell membranes. There is evidence for these changes to be disruptive to cell function, and thus a meaningful contribution to age-related degeneration. Like many of the areas of interest in the study of aging, this has the look of a form of disarray that is downstream of the molecular damage that lies at the root of aging. Nonetheless, it is suggested that supplementing the levels of specific lipids, where they decline with age, may be beneficial enough to be worth the effort.

Lipids are an essential constituent of the cell membrane of which polyunsaturated fatty acids (PUFAs) are the most important component. Activation of phospholipase A2 (PLA2) induces the release of PUFAs from the cell membrane that form precursors to both pro- and ant-inflammatory bioactive lipids that participate in several cellular processes. PUFAs GLA (gamma-linolenic acid), DGLA (dihomo-GLA), AA (arachidonic acid), EPA (eicosapentaenoic acid), and DHA (docosahexaenoic acid) are derived from dietary linoleic acid (LA) and alpha-linolenic acid (ALA) by the action of desaturases whose activity declines with age. Consequently, aged cells are deficient in GLA, DGLA, AA, AA, EPA, and DHA, and their metabolites.

LA, ALA, AA, EPA and DHA can also be obtained direct from diet and their deficiency (fatty acids) may indicate malnutrition and deficiency of several minerals, trace elements, and vitamins some of which are also much needed co-factors for the normal activity of desaturases. In many instances (patients) the plasma and tissue levels of GLA, DGLA, AA, EPA, and DHA are low (as seen in patients with hypertension, type 2 diabetes mellitus) but they do not have deficiency of other nutrients. Hence, it is reasonable to consider that the deficiency of GLA, DGLA, AA, EPA, and DHA noted in these conditions are due to the decreased activity of desaturases and elongases.

PUFAs and their anti-inflammatory metabolites influence the activity of SIRT6 and other SIRTs and thus, bring about their actions on metabolism, inflammation, and genome maintenance. GLA, DGLA, AA, EPA and DHA, and prostaglandin E2 (PGE2), lipoxin A4 (LXA4) (pro- and anti-inflammatory metabolites of AA respectively) activate/suppress various SIRTs, PPAR-γ, PARP, p53, SREBP1, intracellular cAMP content, PKA activity, and PGC1-α. This implies that changes in the metabolism of bioactive lipids as a result of altered activities of desaturases, COX-2 and 5-LOX, 12-LOX, and 15-LOX (cyclo-oxygenase and lipoxygenases respectively) may have a critical role in determining cell age and development of several aging associated diseases and genomic stability and gene and oncogene activation. Thus, methods designed to maintain homeostasis of bioactive lipids (GLA, DGLA, AA, EPA, DHA, PGE2, LXA4) may arrest aging process and associated metabolic abnormalities.



I found 2 quotes of relevance to our cause:

Erich Fromm:
"If the individual lived five hundred or one thousand years, this clash (between his interests and those of society) might not exist or at least might be considerably reduced. He then might live and harvest with joy what he sowed in sorrow; the suffering of one historical period which will bear fruit in the next one could bear fruit for him too."
John F. Kennedy, 1962:
I am reminded of the story of the great French Marshal Lyautey, who once asked his gardener to plant a tree. The gardener objected that the tree was slow-growing and would not reach maturity for a hundred years. The Marshal replied, "In that case, there is no time to lose, plant it this afternoon."

Posted by: thomas.a at March 8th, 2021 10:10 AM

Fish oil, flax seed, walnuts etc? Any particular protocol for this?

Posted by: Chuck Frasher at March 15th, 2021 4:16 PM

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