14 replies to this topic

[MikeDC]

Scientists have spent decades studying aging caused by oxidative stress and damage accumulation. 4-HNE is a toxic waste from oxidative damage, especially related Linoleic acid oxidation. But no one can conclusively confirm that 4-HNE is the root cause of aging. I am sure you all have heard that OSKM and OSK reprogramming cured blind mice, monkeys. It is in clinical trial. Ryan Lu studied OSK therapy further and found that what cured the blind sight is due to GSTA4 over expression. GSTA4 is a well known gene that clears 4-HNE with glutathione as cofactor. GSTA4 is sufficient and required to remove 4-HNE and restore RPE function. So this paper has shown that 4-HNE is the most important factor in aging.

https://www.biorxiv.....08.30.673239v1


So it has been proven that we can rejuvenate cells by removing 4-HNE. There are perfect supplements just for this purpose. Sulforaphane can upregulate NRF2 which upregulate GSTA4. There are studies that show Sulforaphane can increase GSTA4 by a few hundred percent. 100mg/kg glycine and NAC has been proven to increase glutathione by a significant amount. So combining these 3 together could replicate OSK reprogramming’s rejuvenation effect. If you want the references you can ask AI on Google. I think this is the most significant finding in our hunt for why we age and how to slow it down.

Outside of this I want to tell people again, liposomal CaAKG has tremendous aging reversal effects. I feel like I am at least 20 years younger after taking it for 3 years. If you combine these two schemes, age reversal is reality. I am going to add Sulforaphane and glycine plus NAC to my daily supplement soon. Fully expecting to get even younger.

[MikeDC]

The general safe upper limit for daily oral N-Acetylcysteine (NAC) supplementation is typically considered to be 3,000 mg per day, though most standard and effective doses range from 600 mg to 1,200 mg per day.Standard and High DosagesStandard Daily Dose: 600 mg to 1,200 mg split into one or two doses is commonly used for general antioxidant and respiratory support.Supervised Maximum Dose: Clinical studies and therapeutic protocols safely utilize up to 2,400 mg to 3,000 mg per day for specific respiratory or psychiatric conditions under medical supervision.Toxicity Threshold: Doses exceeding 3,000 mg daily significantly increase the likelihood of side effects without added clinical benefit, and total cysteine intake should stay well below toxic limits.

[MikeDC]

There is no clinical evidence that standard doses of N-acetylcysteine (NAC) cause damage to the blood-brain barrier (BBB) in humans.Current Evidence on NAC and the Blood-Brain Barrier. Low Human Data: No human clinical trials or standard medical data link standard oral or intravenous NAC administration to structural or functional breakdown of the blood-brain barrier.Limited Permeability: NAC has relatively poor and limited permeability across the human blood-brain barrier due to its low bioavailability (often around 6% to 10%) and negative charge at physiological pH.Preclinical Animal Findings: Isolated animal studies (such as in specific stroke-prone or genetically hypertensive rodent models) have raised theoretical questions about high doses or specific pathological states altering barrier dynamics, but these findings have not translated to evidence of human BBB damage during standard use.Protective Effects: In several preclinical models of brain injury or inflammation, NAC actually helps protect or restore vascular and blood-brain barrier integrity by reducing oxidative and nitrosative stress.

Edited by MikeDC, 27 September 2026 - 04:15 PM.

[MikeDC]

In Ryan Lu’s first paper on OSK reprogramming on injured RGC cells, He showed that TET was required to reset epigenetic age to achieve RGC repair. Humans don’t have the ability to regenerate RGC cells no matter how young you are. OSK actually activated a lot more genes far beyond simply reversing methylation patterns to youthful State. Some of the genes tracing back to embryonic development Could be activated. So this experiment is not a prove that you Need to reset epigenetic age to rejuvenate cells to younger
State because regenerating RGC is not something young Or old humans can do. This experiment is not about aging Reversal. It was about repairing damaged RGC using genes
That are not active after birth.

Edited by MikeDC, 28 September 2026 - 12:00 PM.

[Mind]

Have you tested your aging biomarkers? It would be useful to see some numbers.

[MikeDC]

Have you tested your aging biomarkers? It would be useful to see some numbers.

I know my insulin resistance is gone. My blood sugar drops to 80 and 90 range a few hours after meal. Prostate is 20 year better. I am certain that liposomal CaAKG has strong age reversal effects. Now I am adding Sulforaphane and Glycine plus NAC. But I can’t tolerate NAC well because it is too acidic. It upset the stomach. Not sure why they don’t sell NAC salt. I had problems with AKG also. So turned to liposomal which doesn’t upset stomach.

[Mind]

Thanks for all of the supplement detail you have provided. I am glad to hear how you feel younger now. I might have to try CaAKG.

[MikeDC]

Thanks for all of the supplement detail you have provided. I am glad to hear how you feel younger now. I might have to try CaAKG.

I use the NEXTDIA liposomal CaAKG. You can take double dose. Two in the morning and two in the afternoon.

[MikeDC]

Before Ryan Lu publish another preprint, I am mentioning ALDH4A1 which is also an important enzyme to clear 4-HNE. It is NAD+ dependent, so 300mg Niagen might be useful. Selenium also helps ALDH4A1. Life Extension Multivitamins has 200 ug of selenium.

[MikeDC]

Since Niagen is getting expensive it doesn’t have a big impact. Non flushing Niacin is cheaper and have a long half life.

[MikeDC]

Since Niagen is getting expensive it doesn’t have a big impact. Non flushing Niacin is cheaper and have a long half life.

Sorry. Slow release or no flushing Niacin are not good. Take Niagen or NAM.

[MikeDC]

A new trial of NR on Parkinson’s disease, showed 1,000mg is harmful. People shouldn’t take high doses of Niagen.

I accidentally found that Bilberry extract can up regulate NRF2 which can upregulate GSTA4. This is cheaper option than buying Sulforaphane.

[MikeDC]

More interesting details of how rejuvenation can be accomplished through supplements. Sulforaphane, glycine, NAC work together through GSTA4 and Glutathione to up regulate first Yamananka factor OCT4. OCTA4 activate genes to rejuvenate cells. In addition
CaAKG is also an important component of OCT4 activation through TET pathway.

[MikeDC]

It is taking 50 days for OSK therapy in cell studies. In vivo will take even longer. Since supplements are weaker, it make take a couple of years before you can feel the rejuvenation effects.

[pepsseeker618]

been on semaglutide for about a year now and one thing i noticed is my inflammation markers dropped a lot on my bloodwork, which tracks with the research on glp-1s reducing oxidative stress. curious whether that would translate to lower 4-hne levels too since lipid peroxidation seems to be right at the center of this whole discussion. either way, i feel noticeably better on it than off, for what it's worth