How to reduce brain decline with age (or maximize mindspan)

akc-important-threads
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Also see the guide I wrote at https://forum.longevitybase.org/t/guide-to-living-longer-alex-k-chen - almost everything here (including healthy diet) is relevant for mindspan. Will highlight more salient mindspan-related content here. Keep in mind mice mostly die of cancer, not brain diseases (cancer and Alzheimer’s are also ANTIcorrelated), so this reduces some of translatability of mouse models to brain aging.

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THE INDEX of Alex K. Chen aging content
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VASCULAR AGING IS SUPER-IMPT Counteracting age-related VEGF signaling insufficiency promotes healthy aging and extends life span | Science

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Google super-ager memory research

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Get Nfl protein measured - https://www.frontiersin.org/articles/10.3389/fneur.2019.00338/full

(Biological age in healthy elderly predicts aging-related diseases including dementia | Scientific Reports ) - tho expensive

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neurofeedback! afvaf afaf

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NGF eyedrops!

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POSSIBLE, needs more info: Edaravone - Wikipedia

https://www.nature.com/articles/s41380-021-01159-1 also needs more evidence.’

novel nootropics - https://www.reddit.com/r/Biohackers/comments/loxe4d/nootropics_discord_group_for_new_advanced/

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=> bigger dendritic spines also decrease less w/age than smaller dendritic spines

https://www.quora.com/Is-it-true-that-the-more-you-use-the-brain-more-agile-the-brain-it-becomes/answer/Alex-K-Chen

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Exercising + playing RTS games when older (esp Sins of a Solar Empire/Rise of Nations can help). Strategy-Based Video Games May Improve Older Adults' Brain Function | American Association for the Advancement of Science

FOLLOW ALL OF KENNETH HAYWORTH

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it’s worth looking up Wallerian degeneration - Wikipedia / https://www.nature.com/articles/nrn3680 - you want to keep NMNAT2 high. Neurons tend to shrink/shrivel rather than die. They are unique from other tissue in that they don’t divide (though they do lose A LITTLE bit of telomere) and how their synaptic/axonal properties ARE affected by age in a way very different from other tissue (in particular, larger spines decline less w/age), and processes that maintain spine size/density tend not to be the same processes that affect aging process in other tissues

also note hypothalamic inflammation is one thing that often makes people unable to control their hunger over time, DON’T EAT TOO MUCH, b/c ROS from feeling full is PRECISELY what controls hypothalamic inflammation.

also too much calcium is bad. Mg/Ca ratio is good to increase. Diffuse axonal injury - Wikipedia

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POSSIBLY interesting (but not the most important thing): https://elifesciences.org/articles/62048
Repair of Mitochondrial Recycling Defect Linked to Parkinson’s Disease - Neuroscience News

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ALCOHOL is INTERESTING. higher levels are undoubtedly bad, but lower levels can promote glymphatic clearance - Alcohol promotes waste clearance in the CNS via brain vascular reactivity - PubMed (needs more info)

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Kaempferol is interesting - high concentration in capers

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https://academic.oup.com/aje/article/164/9/898/87190 possibly, tho effect size is not large

Guide to Living Longer (Alex K. Chen)
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this is so good - https://drgoodenowe.mykajabi.com/products/dr-goodenowe-s-educational-seminars

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Supplementation with ProdromeNeuro was observed to elevate blood DHA-plasmalogen levels. The increase in blood DHA-plasmalogens correlated with a decrease in malondialdehyde levels (r=-0.5, p=7.2e-07) and an increase in catalase activity (r=0.28, p=0.008). Superoxide dismutase activity was increased in persons with low baseline activity (p=0.017).

To access the FREE seminars with full presentations and videos please visit Dr. Goodenowe’s resource site here. This is the article for seminar C106, Supplements (Series C).

ProdromeNeuro is a plasmalogen supplement designed to specifically elevate DHA plasmalogen levels. An escalating dose study was performed in 22 persons (11M/11F) diagnosed with various degrees of cognitive impairment to determine the optimal dose for elevating blood plasmalogen levels.

In addition to clinical evaluations of cognition and mobility, blood samples were collected at baseline and after each month of supplement dosing for biomarker analyses.

The escalating dosing of ProdromeNeuro was performed as follows:

Month 1 – 1ml/day (900mg/day – one bottle of ProdromeNeuro)

Month 2 – 2ml/day (1800mg/day – two bottles of ProdromeNeuro)

Month 3 – 2ml/day (1800mg/day – two bottles of ProdromeNeuro)

Month 4 – 4ml/day (3600mg/day – four bottles of ProdromeNeuro)

Month 5 – 0ml/day (0mg/day – zero bottles of ProdromeNeuro)

Blood DHA-Plasmalogen levels were observed to be increased in all participants in a dose-dependent manner. After month 1 there was a 30% increase, after months 2 and 3 there was a 60% increase and after month 4 there was a 90% increase in the target DHA-plasmalogen levels. Persons with low baseline DHA-plasmalogen levels (quartiles 1 and 2) experienced a greater increase in blood DHA-plasmalogen levels (50%, 90%, and 120%, respectively). When blood DHA-plasmalogen levels were expressed relative to an endogenous non-DHA phosphatidylethanolamine, the relative increase in the target DHA plasmalogen levels was more pronounced.

The oxidative stress cascade begins with the formation of the superoxide radical resulting from a cellular insufficiency in recycling NADH back to NAD by the mitochondrial electron transport chain. A build-up of NADH beyond the intracellular capacity to recycle NADH by alternative, non-oxidative, anaerobic mechanisms leads to the export of free electrons to the extracellular environment by NAD(P)H oxidase (NOX). These electrons combine with molecular oxygen to form the superoxide radical. Superoxide is neutralized to molecular oxygen and hydrogen peroxide by superoxide dismutase both inside and outside of the cell. Hydrogen peroxide, in turn, is neutralized into molecular oxygen and water by multiple mechanisms such as catalase, glutathione peroxidase or by chemical neutralization by plasmalogens. The failure of the antioxidant system to neutralize hydrogen peroxide results in hydrogen peroxide reacting with superoxide to form the hydroxyl free radical. The hydroxyl free radical reacts with polyunsaturated fatty acids in biological membranes to form lipid peroxides. These lipid peroxides are the primary chemoattractants for inflammatory immune cells. Malondialdehyde is a biomarker of lipid peroxidation and thus represents and quantifies the oxidative stress load on biological systems. In order to assess the effect of elevating blood DHA-plasmalogens on the oxidative stress load on the participants in the trial, malondialdehyde levels, catalase and superoxide dismutase activity and C-reactive protein levels were measured in all participants at baseline and at the end of months 3-5. Although these biomarkers are quantitatively measured, they each have biological floor levels that represent a “healthy state” which cannot reasonably be improved upon. Accordingly, in addition to evaluating the effect of ProdromeNeuro on all participants, participants were also grouped into either low (Q1,Q2) or high (Q3,Q4) subgroups and evaluated accordingly.

ProdromeNeuro supplementation reduced malondialdehyde levels in all participants by 32% (p=0.028) and by 46% (p=0.002) in persons with high baseline malondialdehyde levels. Overall, malondialdehyde levels were negatively correlated with blood DHA-plasmalogen levels (r=-0.5, p=7.2e-07)

ProdromeNeuro supplementation increased catalase activity to 186% (p=0.014) of baseline levels in participants and to 240% (p=0.02) in persons with low baseline catalase activity. Overall, catalase activity was positively correlated with blood DHA-plasmalogen levels (r=0.28, p=0.008)

ProdromeNeuro supplementation increased superoxide dismutase activity (p=0.017) only in persons with low baseline superoxide dismutase activity.

Of the 22 participants, only 4 had baseline C-reactive protein levels greater than 1.0. All four of these participants had low baseline DHA-plasmalogen levels. All four of these participants exhibited a decrease in CRP by greater than 0.5 units and in two of the participants CRP levels decreased to less than 0.5.

The results of the oxidative stress biomarker analyses indicate that increasing blood DHA-plasmalogen levels using ProdromeNeuro has a profound positive effect on oxidative stress biomarkers.

ProdromeNeuro was well tolerated at all dosages and no adverse reactions were observed or reported.

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