NEW PAPER: DNA methylation entropy is proportional to chronological age, supporting the Information Theory of Aging, the concept that our bodies are biological computers running on software that becomes corrupted over time but can be reinstalled...🧵 aging-us.com/article/206220… Somatic cells in the human body share the same genome, yet they must differentiate into diverse cell types to perform the vast array of tasks

12 lessons students learn in the Sinclair Lab:

Lesson 1. Write the way you speak Lesson 2: Avoid unnecessary jargon when possible. It only makes you seem less intelligent

Here’s a list of all major sources of DNA damage in our daily lives & how to avoid them.. 🧵

https://twitter.com/thebcmessenger/status/1902840877543985618

Of all the various types of DNA damage, double stranded DNA breaks (DSBs) are believed to be the most potent cause of aging. Here are 2 mice, one that’s experienced ~3x more DSBs than its sibling

NEW STUDY: Food and drinks that associate with healthy aging, better memory & a longer, disease-free life & those that don’t. Surprising results… 🍷🍟 🧵 How to read the figures in this new paper: green means heathy, red means unhealthy. Column 1 is healthy aging, 2 is cognitive function and so on…

Polyphenols aren't just antioxidants. They signal to the body - defend and heal. New evidence indicates that polyphenols might prevent cancer by modulating small RNAs... a thread 🧵 In the 1990's, antioxidants were all the rage. Today, we know so much more, though the food and beverage industry still promotes antioxidants as though they were the most important thing...

NEW STUDY: SIRT5, the neglected mitochondrial Sirtuin, which depends on NAD, is shown to slow muscle aging 🧵 @NatMetabolism When SIRT5 was delivered to skeletal muscle it enhanced physical performance and alleviated age-related muscle dysfunction

NEW STUDY: 50-80% of us will experience back pain in our lives. OSK is shown to alleviate cellular senescence 🧟 & back pain 🐀 suggesting epigenetic reprogramming might address this major economic burden & #1 cause of human disability… 🧵 OSK stands for Oct4, Sox2 and Klf4, three genes that are part of a set that Shinya Yamanaka showed can make adult cells into pluripotent stem cells. The gene products are transcription factors that control how genes are turned on and off (during embryogenesis)

GLP1 receptor agonists are looking like longevity drugs. A new study reports that drug-induced improvements in bone mass are mediated by the NAD-dependent SIRT1 enzyme.
If so, could NAD boosters work with GLP-1 drugs? Some thoughts...🧵 This new study is consistent with studies showing NMN, an NAD booster & SIRT1 activator, improves bone mass in mice

Imagine being able to predict or detect diseases with a cheek swab? NEW STUDY finds a cheek clock associates with 33 conditions:

1. Various cancers
2. Aging
3. Prediabetes
4. Depression
5. Lung fibrosis
6. Chemicals
7. Fatty liver

How is it possible? 🧵
tinyurl.com/4db5r2tc I am proud to have worked with the dream team that developed this next-gen epigenetic clock using buccal cheek swab data, one of the largest clock studies...

10 quotes from Thomas Kuhn that changed my life and have never been more relevant:

1. The competition between paradigms is not the sort of battle that can be resolved by proofs

(Scientists, read that again) 2. When paradigms change, the world itself changes with them

The mTOR inhibitor Sapanisertib is a putative longevity molecule that makes human skin cells & prematurely old fish healthier

Combined with metformin (a putative longevity drug), 79% of human patients with advanced or metastatic solid tumors achieved disease control. Promising results.

Could S+M be a longevity combo and who owns it? 🧵
tinyurl.com/bdbkx2re Metformin’s metabolic benefits might counterbalance Sapanisertib’s potential side effects, like insulin resistance, seen in some patients taking the mTOR inhibitor rapamycin
frontiersin.org/journals/neuro…

NEW STUDY: Intermittent fasting (IF) significantly alters the microbiome of mice, with reductions in the gut production of obeticholic acid, a bile acid that induces expression of gut-derived hormones, and an increase in N-acetylglycine production

Why is this interesting? 🧵 A couple of studies have identified serum N-acetylglycine (NAG) as a correlate of weight status and see an inverse relationship between N-acetylglycine and BMI
Link to microbe paper: …ritionandmetabolism.biomedcentral.com/articles/10.11…
Link to NAG paper: journals.plos.org/plosone/articl…

Cool if true: Intermittent fasting BEFORE conception in rats apparently causes offspring to have accelerated development, including faster whisker growth, reflexes, ear unfolding & tooth eruption

So, does a mother's diet impact her eggs & therefore her babies' future? 🧵 It's already been reported that caloric restriction (CR) with adequate nutrition during pregnancy affects offspring in seemingly positive ways, e.g. antioxidant defenses
Of course this is not recommended by nutritionists, its simply an experiment to test lasting epigenetic effects
sciencedirect.com/science/articl…

NMN treatment for 4 weeks improves egg quality & restores fertilization rates in female mice with chemo-damaged eggs… 🧵 This paper is consistent with our joint-study showing restoration of egg quality and fertility of old female mice 🐁 @LindsayWu_UNSW

Aortic aneurysms are known as the “silent killer”. Rupture of a bulging vessel can kill you in minutes. New study links low NAD+ to the formation of aneurysms.

So,
How do you prevent them?
Can you detect them?
Might taking NAD boosters help?

A personal thread... 🧵 A few years ago, my father's best friend who traveled the world with him, Tom, had a aortic aneurysm rupture

Despite resveratrol's health and longevity benefits in animals, results in humans have been mixed. Why?

New article suggests it's because resveratrol lacks water-solubility & provides solutions to increase its effectiveness in people... 🧵 Resveratrol extends lifespan in numerous species, including bees! The new review summarizes the most significant effects, problematic properties, and approaches to overcoming its limitations

A student asked, why does cell repair turn off when times are good? Why not keep them on all the time?

The answer reveals how to live a long, healthy life...🧵 During periods of abundance, organisms benefit from storing energy for future adversity, instead of using it for long-term health - hence the obesity epidemic...

Ergothioneine from mushrooms increases muscle size & endurance in rats by raising NAD levels

So, what is ergothioneine and where is it found?
@Cell_Metabolism dlvr.it/THVRKK Ergothioneine (ET) is a sulfur-containing amino acid, discovered over 100 years ago. Humans and animals can’t make it—we rely entirely on diet to obtain it. The yellow ball is the sulfur

The body's self-cleaning mechanism that recycles old proteins requires spermidine, a remarkable molecule that prevents hair loss in mice and extends the lifespan of every species tested

So what is spermidine and does it work in humans? 🧵 Spermidine was discovered in 1678 by Antonie van Leeuwenhoek, the Father of Microbiology, in his own semen - hence the name. Actually, spermidine is found in all species, even fungi and plants🪴

Congrats 👏

Here’s what diseases activation of NAD-dependent SIRT3 might prevent or treat - and how to activate it…

https://twitter.com/dr_singularity/status/1881041189224235011

I’m unaware of a study where SIRT3 activation extends rodent lifespan but it is known to protect cells and mice from:
1.Oxidative stress
2.Mitochondrial dysfunction
3.Metabolic disorders
4.DNA damage/senescence
5.Programmed cell death

A 50-year-long study of twins finds exercise may not be as important for longevity as we think

A thread...🧵 It's almost heretical to say it but this study questions whether excessive exercise is a good thing and if it's even worth it. Let's look at the data...