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David Sinclair Profile picture
@davidasinclair
Oct 29, 2024 • 7 tweets • 2 min read • Read on X
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Effect of longevity interventions on epigenetic clocks:

Strongest:
1. Arthritis therapy/anti-TNFa
2. Metformin
3. HBOT
4. AC-11
5. Bypass
6. Ketamine
7. Vegan/Mediterranean

No effect:
1. Rapamycin
2. Omegas
3. Exercise
4. Vitamin B
5. CR/IF
6. Ozempic
7. Follistatin
More ⬇️ Image
DNA methylation (DNAme) age reductions. Red asterisks represent statistical significance
* P<0.05; ** 0.01; *** 0.001 Image
No effect on DNAme age: Image
Negative effect on DNAme age: Image
Blood biomarkers that serve as proxies for DNAme age and diets:

CystatinC - kidney function
HBA1c - glucose / diabetes
CRP - inflammation/ heart disease
ALK - liver / bone health
Triglycerides - serum fat / heart disease Image
From the Longevity Interventional Studies Community & lab of Albert Higgins Chen @YaleMed. The manuscript can be accessed @biorxivpreprint and has not yet been peer reviewed and might change during this process - like defining what “ART” is 🙏
biorxiv.org/content/10.110…
@YaleMed @biorxivpreprint Why might ketamine change DNAme? Ketamine can reduce methylation at specific sites within the BDNF gene, potentially improving brain health, which might positively affect other cells and blood biomarkers. Or maybe it acts via peripheral nerves 💪

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More from @davidasinclair

David Sinclair Profile picture
Oct 7
Statistically, you should not exist:

– Life-friendly universe: 1/10⁶⁰
– Earth + moon: 1/10⁹
– Multicellular life: 1/10⁴
– Intelligence & civilization: 1/10⁹
– Your genome: 1/70 trillion

You’ve already won the lottery 10 times in a row. Ignore small people & enjoy!
Equivalent odds: winning the Powerball jackpot 10 times in a row
Flipping 272 heads in a row
Read 7 tweets
David Sinclair Profile picture
Oct 4
DNA breaks from cosmic rays disrupt the epigenome and release virus-like retrotransposons. Not wild theory. Fact

X-rays and CT scans probably do too but no one talks about it
This study in 2008 was the first evidence for the information theory of aging in mammals - the idea that DNA breaks and other major stresses cause chromatin modifiers like SIRT1 to relocate, which disrupts the epigenome & changes the expression of genes in ways that cause aging Image
Just re-read this paper and I’ve realized it was 15 years ahead of its time. Still is
Read 4 tweets
David Sinclair Profile picture
Oct 2
Some plant polyphenols (resveratrol, quercetin & berberine) turn out to be dual modulators of both SIRT1 & GSK3b - important pathways for neuroprotection & epigenetic age resets... 🧵Image
In 2008, we showed movement of the NAD-dependent enzyme SIRT1 away from regulated genes to DNA breaks (which happen every day in every cell) is a key process in the loss of epigenetic information that we have proposed leads to aging and diseases
cell.com/fulltext/S0092…Image
And in 2023, we showed GSK3b inhibitors are a key component of epigenetic age reversal cocktails, in vitro
aging-us.com/article/204896Image
Read 5 tweets
David Sinclair Profile picture
Oct 1
Can cheek swab DNA reveal meaningful signals about your health, diseases and biological age?🏃‍♂️🏃‍♀️🧵... Image
Background: DNA methylation (DNAme) is a chemical modification of DNA on the "Cs" in DNA, which changes over time, the rate of which depends on how healthy you live over the course of your life... ⏰ Image
Smoking and obesity accelerate DNAme changes, and healthy diets slow them. We can read these changes using DNA sequencing or DNA hybridization chips. This is how we arrive at DNAme age clocks... Image
Read 16 tweets
David Sinclair Profile picture
Sep 28
Exciting new paper @nature that could explain why inflammation rises as we age and why healthy diets and exercise suppress inflammation 👏 🧵 Image
Various mitochondrial stressors, such as pathogen infection and metabolic deficiencies, trigger the release of mtDNA into the cytosol and an inflammatory response, but why? Image
Under certain circumstances, including in senescent cells, there are decreased levels of deoxyribonucleotide triphosphates (dNTPs) for making DNA, with a corresponding increase in the levels of ribonucleotide monophosphates (rNMPs)… Image
Read 9 tweets
David Sinclair Profile picture
Sep 22
NEW STUDY: The amino acid L-theanine, first isolated from green tea in the 1940s, is used to improve mood and sleep 🍵 Study in mice finds L-theanine suppresses metastasis of prostate cancer, the second most common cause of death in men worldwide... 🧵 Image
L-theanine is known to reduce inflammation, stress and anxiety, among other effects. It is primarily found in tea leaves, especially green & black. Also in supplements. Common doses are 100 - 400 mg/d Image
A great way to get L--theanine is a green tea matcha = 30-140 mg L-theanine 🍵

I drink 1-3 double-scoop green tea matchas. I use organic ceremonial grade tea, frothed almond milk, allulose, and dont burn it with boiling water. Learned from @chefserenapoon Image
Read 5 tweets

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