David Sinclair Profile picture
Professor @Harvard researching why we age & how to reverse it. Author & host of Lifespan. Mission: Extend healthy life for all. Views are entirely his own 🙏✌️
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Mar 26 7 tweets 3 min read
NEW STUDY: Food and drinks that associate with healthy aging, better memory & a longer, disease-free life & those that don’t. Surprising results… 🍷🍟 🧵 Image 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… Image
Mar 23 8 tweets 3 min read
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 🧵 Image 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... Image
Mar 19 5 tweets 1 min read
NEW STUDY: SIRT5, the neglected mitochondrial Sirtuin, which depends on NAD, is shown to slow muscle aging 🧵 @NatMetabolism Image When SIRT5 was delivered to skeletal muscle it enhanced physical performance and alleviated age-related muscle dysfunction Image
Mar 13 8 tweets 3 min read
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… 🧵 Image 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)
Mar 12 10 tweets 3 min read
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...🧵 Image This new study is consistent with studies showing NMN, an NAD booster & SIRT1 activator, improves bone mass in mice Image
Mar 8 13 tweets 4 min read
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... Image
Mar 3 11 tweets 4 min read
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) Image 2. When paradigms change, the world itself changes with them Image
Mar 1 13 tweets 3 min read
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…Image
Feb 26 5 tweets 2 min read
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? 🧵 Image 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…
Feb 17 11 tweets 4 min read
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? 🧵 Image 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…Image
Feb 11 5 tweets 2 min read
NMN treatment for 4 weeks improves egg quality & restores fertilization rates in female mice with chemo-damaged eggs… 🧵 Image This paper is consistent with our joint-study showing restoration of egg quality and fertility of old female mice 🐁 @LindsayWu_UNSW Image
Jan 26 14 tweets 4 min read
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 Image
Jan 26 11 tweets 4 min read
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 Image
Jan 25 7 tweets 2 min read
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... Image
Jan 23 26 tweets 7 min read
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/THVRKKImage 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 Image
Jan 21 21 tweets 8 min read
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🪴Image
Jan 19 9 tweets 3 min read
Congrats 👏

Here’s what diseases activation of NAD-dependent SIRT3 might prevent or treat - and how to activate it… 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 Image
Jan 18 20 tweets 5 min read
A 50-year-long study of twins finds exercise may not be as important for longevity as we think

A thread...🧵 Image 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... Image
Jan 16 10 tweets 4 min read
You are what you eat—but not for the reasons you might think🧬 Here’s how your diet influences your genes... 🧵 Image In bacteria, whether a gene is switched on or off is affected by the fluctuating environment. Complex organisms like us are too, but we regulate our DNA in much more complex ways, adding and subtracting chemicals from chromosomes to control genes... Image
Jan 15 12 tweets 4 min read
The largest and longest clinical trial comparing the effects of lifestyle changes vs. medicines on glucose control, inflammation, blood pressure & cholesterol over 24 weeks. The lifestyle changes won - hands down

Here's what they found...
tinyurl.com/yjev6dbtImage The clinical trial was conducted in the Marshall Islands, which has the seventh-highest diabetes prevalence globally. There were 169 participants... Image
Image
Jan 14 14 tweets 5 min read
What are epigenetic clocks and are they in fact useful?
A thread 🧵 One of the most profound biological insights of the past few decades has been the demonstration that various forms of biological age are quantifiable Image