Sinclair says Ana Maria Cuervo reported that triggering chaperone-mediated autophagy in old mice extends their lifespan by 35 percent.
“if you trigger this process in an in an old mouse, it lives 35% longer.”
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David Sinclair
2 episodes · 34 quoted claims
Sinclair says old female mice, infertile since about twelve months, regained fertility about six weeks after receiving NMN.
“Gave them NMN, and I think it was only six weeks later, they had offspring, they became fertile again”
Sinclair says Manuel Serrano's lab in Spain found that excess iron increases the number of senescent cells, meaning inflammatory 'zombie' cells that build up with age.
“Manuel Serrano's lab has found that, uh, excess iron will increase the number of senescent cells in the body.”
Sinclair says he has taken a statin since age 29 because of a family history of heart disease and cholesterol above 300.
“I've been taking a statin since I was twenty nine, and that's cause I forced my same doctor to give me the statin.”
Sinclair says Peter Attia pointed him to a study that he believes shows dietary cholesterol has almost no effect on blood cholesterol.
“our friend Peter Attia, uh, brought to my attention recently a new study that I think definitively said that dietary cholesterol has almost zero impact on blood cholesterol levels.”
Sinclair says that altering resveratrol so it was no longer an antioxidant still extended yeast lifespan, suggesting antioxidant activity was not the mechanism.
“If we changed one atom to make it not an antioxidant, guess what? It still worked fine.”
Sinclair said the eye age-reversal therapy would be tested in monkeys first, with a first human patient expected in 2022 or early 2023 to try to restore vision.
“we're going to be testing the treatment on, um, monkeys, uh, for just for safety reasons, uh, and then the first patient should be done sometime in 2022, early 2023, and we're gonna try to recover blindness.”
Sinclair says the eye therapy delivers genes into the retina that are switched on with the antibiotic doxycycline for four to eight weeks in mice, restoring vision.
“The genes go into the retina and we can turn it on with a drug called doxycycline, and we do that in the mice for four to eight weeks.”
Sinclair says he and Ray Kurzweil published the metabolic winter hypothesis, proposing that humans were historically often hungry or cold and now rarely are.
“We published what's called the metabolic winter hypothesis, which is few tens of thousands of years ago, we were either hungry or cold or both”
Sinclair says Dongsheng Cai showed that reducing hypothalamic inflammation in mice maintains GnRH expression and extends lifespan.
“it's been shown by Dongsheng Kai, um, at Albona, Albertson College of Medicine, that if you inhibit inflammation in the hypothalamus in a mouse, it will increase or maintain the expression of what's called GnRH”
David Sinclair says his lab's age-reversal technology has cured blindness in animals including primates.
“What we're finding in animals, that includes primates, is that we can cure things that have previously been impossible, including blindness, by the way.”
Sinclair's planned eye therapy introduces three genes into the optic nerve and activates them for six to eight weeks.
“we're introducing a set of three genes into this optic nerve at the back of the eye and turning them on for six to eight weeks.”
An independent lab used Sinclair's three-gene technology in very old mice by injecting it into the vein.
“They injected into the vein of the mouse the old mice, uh, and turned it on in these really old mice.”
Sinclair recalls futurist Ray Kurzweil predicting the singularity around the 2040s, though Sinclair is skeptical.
“Ray Kurzweil said, it's coming soon.”
Sinclair says James Watson, co-discoverer of the DNA structure, died the month before the interview.
“my friend, uh, Jim Watson, uh, died recently, uh, last month, who he and his colleague discovered that D N A”
Sinclair's information theory of aging holds that loss of epigenetic control information, not DNA itself, drives aging.
“the information theory of aging states that the information that's in a cell, which includes the D N A, but actually more importantly for aging, is the control systems, the epigenome.”
Sinclair's lab created 'ice mice', named for inducible changes to the epigenome, to test whether DNA breaks cause aging.
“We call them the ice mice. Ice stands for inducible changes to the epigenome, and we were able to induce these changes.”
The ice mice carried a slime mold gene, activated by tamoxifen, that cuts DNA without causing cancer or mutations.
“turned on a gene from a slime mold, something you might find in the forest, that breaks D N A of the mouse, but does it in a way that doesn't cause cancer or mutations”
Sinclair says the treated mice aged much faster than untreated twins, with gray fur and age-related diseases about ten months later.
“they were super gray and super old and had all the diseases of aging 50 faster than their twins that we didn't treat.”
Sinclair cites a Harvard long-term study of World War II veterans in saying healthy habits can add about 14 years of life.
“This is based on a study that came out from Harvard, a long-term study of the lifespan of World War II veterans.”
Sinclair says the bristlecone pine is the longest-lived tree and is poisonous, so little eats it.
“the longest lived tree in the world, it can live many thousands of years.”
Sinclair says the US government blocked a foreign investment of over $100 million in a company he serves on the board of, citing the sensitivity of age-reversal technology.
“A large investment into, uh, the com, one of the companies that I, uh, sit on the board of, was blocked because the U S government claimed that the technology was too dangerous”
Sinclair says a gram of NMN swallowed by a human typically doubles NAD levels in the body.
“When you give a human N M N by swallowing it, a gram of it, you can typ. You typically double the amount of N A D in your body.”
Sinclair says deep protein cleanup through chaperone-mediated autophagy happens after about two and a half to three days of fasting.
“the true, real deep clean cleansing of old proteins and damage damaged proteins happens after two and a half to three days. And it's called chaperone-mediated autophagy.”
Sinclair says one of his 1996 papers raised red wine sales by about 30%.
“One of my papers in 1996 caused red wine sales to go up 30% and stayed up.”
Sinclair says he has taken a statin to lower LDL cholesterol since age 30.
“So I've actually been on a statin to lower my L D L since I was thirty.”
Sinclair says spermidine was first crystallized by Antonie van Leeuwenhoek, which is why it is named for its origin in semen.
“It was crystallized by, I believe, Anthony von Leeuwenhoek, one of the first microscopists and microbiologists.”
Sinclair takes daily baby aspirin despite medical groups no longer recommending it for the average person, citing his high cardiovascular risk.
“I take a baby aspirin every day, even though some doctors um, and some institutions of doctors say, don't take it anymore”
Sinclair says the trial material was manufactured in Europe over about a year at a cost of roughly $10 million.
“We just made a bunch of this in Europe for the clinical trial that's gonna begin.”
Sinclair's gene therapy uses an AAV2 delivery vector designed to target retinal nerves and is said to be ready for human use pending FDA approval.
“It's called an A A V two. Um, long story short, these are ready to go into humans.”
Sinclair's therapy uses the antibiotic doxycycline to switch the three rejuvenation genes on.
“We give them doxycycline. It's used for malaria, it's used for Lyme disease, and we're using it in this case to turn these genes on.”
Sinclair says the company developing the eye therapy is the private firm Life Biosciences.
“The company, people might want to know, it's called Life Biosciences, it's a private company.”
Sinclair says AI was used to screen about 8 billion candidate molecules in search of a pill that reproduces the effect of the three genes.
“We screened about 8 billion candidates using A I, and right now we're doing the bench lab work to see if one of them or more works.”
Sinclair says he thinks there is a better than 50% chance that reality is a simulation.
“I think there's a better than 50% chance that this is simulated.”