Senolytics with DGLA and GLA?
In a comment posted on Fight Aging!, Robert Read says:
"There is a specific fatty acid made in small amounts in the body called dihomo-gamma-linoleic acid or DGLA. It's also present in tiny amounts in the diet. When I gave aged mice larger amounts of DGLA, they went from having quite a few senescent cells to having significantly fewer.
This presents a new therapeutic target. I identified a candidate compound using the DGLA metabolic pathway that works at a dose that is over 1,000 times lower than fisetin, so you can imagine we're quite excited by these results.
Like many biomedical discoveries, it was accidental. DGLA makes anti-inflammatory lipids, which help alleviate conditions such as rheumatoid arthritis. I was studying this aspect of DGLA when I was surprised to discover that it killed senescent cells." He gives this reference.
Doing an Internet search does not show any convenient suppliers of DGLA, but Life Extension sells Mega GLA @ $9.90 for 30 x 400 mg capsules, which also contain 10 mg of sesame lignans. The description says that the sesame lignans is added "to help promote healthy levels of beneficial DGLA. Sesame lignans help inhibit the conversion of GLA into inflammatory arachidonic acid. This, in turn, inhibits the formation of other inflammatory compounds like PGE2 and LTB4 in order to support whole body health."
We have already been taking one Mega GLA cap each evening to enhance autophagy of damaged red blood cells. Perhaps we're also doing some senolytics as a bonus.
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Following up on Senolytics with DGLA and GLA, I found the following in regards to minimizing arachidonic acid being metabolized from DGLA:
One concern related to DGLA, is that it could be further metabolized to arachidonic acid with subsequent pro-inflammatory effects. Human studies have demonstrated that the addition of fish-derived omega-3 EPA in a balanced ratio to GLA, blocks the activity of delta-5-desaturase and prevents elevations in serum arachidonic acid.
Co-ingesting similar levels of EPA and GLA increases cellular membrane content of both DGLA and EPA (precursor to anti-inflammatory eicosinoids). In short, this supplementation strategy successfully maintains the anti-inflammatory capacity of GLA and increases serum EPA, without causing accumulation of arachidonic acid.
GLA-enriched oils are more effectively paired with fish oil rather than flaxseed oil to promote the complementary actions of GLA and EPA.Following that strategy, and considering cost, I plan to take 800 mg EPA from fish oil plus 200 mg GLA standardized from borage oil, and 5mg bioperine. With an expected increase in bioavailability of 200% or more from bioperine, that may result in a little more GLA than I would want. Admittedly its something of a guess. I may not know until next quarterly blood tests if I have the right ratio.
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There is not a lot of specifics in that article, but if it works like other senolytics it may be advisable to use it like other senolytics in intermittent bursts. Perhaps any very short term inflammation wouldn't matter much.
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Dan Nave
Thats good advice. We really don’t know if there might be other unknown side effects.
I am somewhat comforted by an article published in 2012 in Lipids in Health and Disease which states:
“… Recent researches indicated that from rodent to human, oral supplementation of DGLA-enriched oil showed no-observed-adverse-effect. In acute and subchronic oral toxicity tests in rats, DGLA oil, ranging from 500, 1000, 2000 mg/kg to 10 g/kg was orally administered. There was no death in either sex and no toxicological changes in body weight, food consumption, ophthalmological examination, urinalysis, hematological examination, blood biochemical examination, necropsy, organ weight, or histopathological examination…”
Any suggestions and rationale as to what would be a reasonable intermittent schedule?
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