David Sinclair Profile picture
Nov 27, 2024 16 tweets 6 min read Read on X
Humanity is headed off a cliff as infertility becomes the 3rd most common disease of the 21st century, according to @WHO. Why infertility is increasing at such a pace is unclear

A new study may shed light. Microplastics are shown to cause abnormalities in the mobility & structure of sperm🐁 & reduce mitochondria in nurse cells by inhibiting SIRT1-PGC-1a ...
sciencedirect.com/science/articl…Image
20% of couples struggle with infertility (50-60% are male issues). By 2100, 97% of countries will be unable to maintain their population

"The implications are immense...These future trends in fertility rates and livebirths will completely reconfigure the global economy and the international balance of power and will necessitate reorganising societies."
healthdata.org/news-events/ne…Image
Sources of polystyrene microplastics: water, fish, "cosmetic products, drugs, paints, medical & electronic devices. In cosmetics, mostly in face-cleansing products, exfoliating agents for hand washing, and peeling formulas" sciencedirect.com/science/articl…Image
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Article about fertility rates falling @TheLancet thelancet.com/journals/lance…
The general fertility rate in the United States decreased by 3% from 2022 to 2023, reaching a historic low. From 2014 to 2020, the rate consistently decreased by 2% annually. The birth rate for women ages 20–24 (55.4) reached a record low. cdc.gov/nchs/pressroom…Image
"Among the cultural shifts affecting fertility rates, one of the more prominent changes has been Americans delaying or forgoing marriage..." @pewresearch
"Women are marrying later in life, and birth rates for single women are less than half that of those who are married"... Image
"Women are also delaying having children until later in life—part of the reason why fertility rates have dropped among women in their 20s, which has more than offset increases for women in their late 30s and 40s..." Image
Low fertility is likely to affect several major revenue streams in the coming decades... pewtrusts.org/en/research-an…Image
In recent budget proposals or revenue forecasts, several states noted declining fertility. California called out the combination of early retirements that have taken place during the pandemic and lower fertility and migration rates... lao.ca.gov/Publications/R…Image
California’s senior population will nearly double by 2030...“With rising cost of living and an already tight housing market, it could become increasingly difficult for the remaining working-age Californians to support the aging population." ppic.org/publication/planning-for-californias-growing-senior-population/
As income from taxation declines due to fewer people in the workforce. Who will pay for the debt? Image
There are two viable solutions:
1. Slow the birth rate decline
2. Delay aging and keep people in the workforce

Our calculated economic benefits of extending healthspan by 1 year in the USA = $38T nature.com/articles/s4358…
@WHO .@elonmusk is 🎯 about the existential risk of low birthrates
If you like fact-based posts with links to source material, press the follow button☝️
Avoid single-use plastics, bottled water, highly-processed foods, plastic cutting boards, plastic storage containers, warming plastic containers, plastic teabags. Vacuum your living space more often...

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More from @davidasinclair

Mar 16
So great to see the OG work that helped spark the longevity revolution taken to the next level:

New paper confirms two main causes of aging:
1. DNA instability -> epigenetic noise
2. Mitochondrial decline
...independently causing failure of the cell

Is this relevant to us? 🧵 Image
Firstly, Dan Gottschling is a legend, having discovered yeast epigenetic gene silencing at the gender genes (a/alpha), telomeres, and painfully scooped me as a postdoc in 1996 by publishing epigenetic silencing at the ribosomal DNA (rDNA) 😆 ... Image
In my postdoc with Leonard Guarente in the 1990s, we predicted (below in my notebook) then confirmed something strange in aging yeast: tiny circles of "extrachomosomal" DNA accumulating inside old cells Image
Read 25 tweets
Mar 8
Osteoarthritis & back pain affects millions of people. Instead of managing symptoms, imagine rebuilding joints by making them young

New study shows the reprogramming gene combo OSK regrows joints in mice & effect depends on TET2 so it's epigenetic...🧵 Image
While limited to mouse models, these findings add to a growing body of evidence that rejuvenation by epigenetic reprogramming may safely reverse aging-related decline in multiple tissues, or whole body one day Image
These experiments used local AAV-OSK delivery directly into the knee joint. Treated animals showed improved cartilage structure and reduced subchondral bone thickening compared with controls Image
Read 16 tweets
Mar 1
According to ITOA, NAD declines with age, causing epigenetic changes & disease susceptibility

In 2010, we showed NAD-dependent enzyme, SIRT3, protects the heart 🐁

New study says NAD precursor NMN protects the heart via SIRT3 in mice fed a Western diet

Why's that important? 🧵 Image
In the United States alone, about 1 in 5 deaths is due to cardiovascular disease. That’s roughly 700K-900K deaths per year. Globally, cardiovascular disease causes nearly 20 million deaths annually
Metabolic dysfunction is a major driver. In the US, ~40 percent of adults are obese and nearly 1 in 3 adults has metabolic syndrome

Globally, more than 500 million people are living with diabetes
Read 15 tweets
Feb 22
Good news: Another study showing that fasting can help cancer patients. A 16 hour fast enhanced the cancer-killing activity of T cells and synergized with immunotherapy to reduce tumor size, ostensibly by causing cancer cells to release the amino isoleucine... 🧵 Image
In the tumor microenvironment (TME), there was increased isoleucine processing and intracellular acetyl-coA, along with increase expression of genes involved in the starvation response, autophagy
There were also alterations in glutamine metabolism, a known source of energy for cancer cells
Read 9 tweets
Feb 1
New "Cardiometabolic Clock" identifies biomarkers that associate with disease & early death:

1. HbA1c
2. Creatinine
3. Lymphocyte %
4. Urea nitrogen (BUN)
5. Red Cell Dist. width (RDW)
6. Pulse
7. Systolic blood pressure

Now you can calculate your CardioMetAge! Image
Heres the formula: 𝐶𝑎𝑟𝑑𝑖𝑜𝑀𝑒𝑡𝐴𝑔𝑒𝑃𝑟𝑒𝑑𝑖𝑐𝑡 = 0.831320 × 𝑎𝑔𝑒 + 19.5734 × log( 𝐻𝑏𝐴1𝑐 + 1) + 1.77394 × 𝑅𝐷𝑊 + 0.0760217 × 𝑆𝐵𝑃 + 6.18803 × 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 − 0.148076 × 𝑙𝑦𝑚𝑝ℎ𝑜𝑐𝑦𝑡𝑒 𝑝𝑒𝑟𝑐𝑒𝑛𝑡 + 0.218946 × 𝑀𝐶𝑉 + 0.105980 × 𝑝𝑢𝑙𝑠𝑒 𝑟𝑎𝑡𝑒 + 0.0603608 × 𝑃𝑃 + 0.636711 × 𝑈𝐴 + 2.40001 × log( 𝐶𝑅𝑃 + 1) + 0.0283277 × 𝑊𝐶 + 0.0754119 × 𝐵𝑈𝑁 − 101.454
Candidate measures tested in the model: Body composition, waist circumference, waist-to-height ratio, glucose, HbA1c, albumin, ALP, CRP, creatinine, blood urea nitrogen (BUN), UA, lymphocyte percent, mean corpuscular volume (MCV), white blood cell count (WBC), red cell distribution width (RDW), AST, ALT, HDL, triglycerides, total cholesterol, BP, pulse pressure (PP) and pulse rate.
Read 4 tweets
Jan 18
Amazing! Placing mice in low air pressure every other day slows hair loss, weight gain, osteoporosis & extends median lifespan by 12%. Ascribed to the killing of senescent, zombie cells

Could exercise, high altitude, or a drug have similar benefits? Let’s dig in🧵 Image
Firstly, hypobaric (low) pressure should not to be confused with hyper-baric oxygen therapy (HBOT), which is also studied by longevity researchers, though there may be overlapping hormetic mechanisms between the two @NaturePortfolio
I’ve always wondered if living at a high altitude is healthier, but the evidence is weak. Maybe it needs to be pulsed: high pressure -> low pressure -> high pressure -> low pressure to induce hormesis Image
Read 19 tweets

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