David Sinclair On Extending Lifespan

[Ableton]

You should clarify. Are you saying that often the repair job doesn't finish or leaves scars (which I would subscribe to) , or that there is stress/destruction inherent in the regeneration process? The former is prescriptive of higher metabolism to complete the job.

EDIT: You answered this already. It sounds like we're on the same page.

Here's a timely Haidut post that speaks against the "wear and tear" theory:

Low, not high, metabolism creates oxidative stress

From the study: "Some electrons are directly transferred to O2 to generate reactive oxygen species (ROS) in the ETC. The second part of this review discusses the sites of ROS generation in each ETC complex, including sites IF and IQ in complex I, site IIF in complex II and site IIIQo in complex III, and the physiological and pathological regulation of ROS. As signaling molecules, ROS play an important role in cell proliferation, hypoxia adaptation and cell fate determination, but excessive ROS can cause irreversible cell damage and even cell death. The occurrence and development of a number of diseases are closely related to ROS overproduction"

Haidut's comments: "it is low oxidative metabolism (OXPHOS), not high, that causes ROS generation. In other words, it is low OXPHOS that causes aging, not high."
​

These are interesting correlations worth expanding upon. But the ROS angle is elegant because it explains a lot with a single vector.



Without nitpicking or sowing doubt on this point, can both positions be right, that low stress leads to longevity but also low ROS/high metabolism does as well?

agreed with your points about unfinished and scars.

I think that in a vacuum, there is no stress in regeneration. With all the stressors present, there might be.

regeneration of your dna through methylation increases cancer risk for example. Every attempt for that matter, to rejuvenate it, increases it
if this would also be the case without any carcinogenic stressors I don’t know. Are hunter and gatherers far from civilization getting cancer? Serious question
As soon as you are holding meat over fire, or smoking some leaves, you have carcinogenics present
Carcinogenics present = anabolism (necessary for regeneration) comes with increased cancer risk.

i even went as far as theorizing every „stressor“ this forum talks about as a direct or indirect carcinogenic

carcinogenics make catabolism through low metabolism necessary for survival

hypothyroidism is literally a naturally induced chemo therapy on your body. The low temps keep pufa in your tissue more stable, too

the cancer paradox is really weird, because people who look young for their age (before the chemo they are put on by their doc) seem to have higher risk. They are anabolic despite the carcinogenics. For them, there is certainly destruction in regeneration

 

[Tarmander]

All these people obsessed with extending their lifespan by 5 years or 10 years are not even really living

 

[MitchMitchell]

@MitchMitchell and @R J
I think you are speculating so much on other people diet, and making up theories
Edit:

what? I’m asking a question about Roddy’s diet

 

[Summer]

All these people obsessed with extending their lifespan by 5 years or 10 years are not even really living

Exactly. 5 more years at the price of being cold and hungry. Hard pass for me.

 

[sweetpeat]

@R J You were close, but left out the juice and fruit:

This one is more recent:

 

[cjm]

agreed with your points about unfinished and scars.

I think that in a vacuum, there is no stress in regeneration. With all the stressors present, there might be.

regeneration of your dna through methylation increases cancer risk for example. Every attempt for that matter, to rejuvenate it, increases it
if this would also be the case without any carcinogenic stressors I don’t know. Are hunter and gatherers far from civilization getting cancer? Serious question
As soon as you are holding meat over fire, or smoking some leaves, you have carcinogenics present
Carcinogenics present = anabolism (necessary for regeneration) comes with increased cancer risk.

i even went as far as theorizing every „stressor“ this forum talks about as a direct or indirect carcinogenic

carcinogenics make catabolism through low metabolism necessary for survival

hypothyroidism is literally a naturally induced chemo therapy on your body. The low temps keep pufa in your tissue more stable, too

the cancer paradox is really weird, because people who look young for their age (before the chemo they are put on by their doc) seem to have higher risk. They are anabolic despite the carcinogenics. For them, there is certainly destruction in regeneration

Dig it. Good points, I'm resonating.

The bit about cooked meat/leaves reminds me of the Instincto Diet (aka Anopsology) developed by Guy Claude-Burger:

_Is anyone else currently coming out against cooking?

o Charges are coming up all over. In the United States, for instance, a cancerologist by the name of Ames devised a method intended to rate the effects of dietary carcinogens. He managed to assess that eating ordinary cooked food leads to an intake of carcinogens tantamount to smoking 40 cigarettes a day. If the food is grilled, which some believe is healthier, one can clock up to a hundred cigarettes a day!

...

Unfortunately, since it takes more like 24 or 48 years to kill you off with the slow relentlessness of arterial sclerosis, how could you possibly make the connection?​

 

[R J]

@MitchMitchell and @R J
I think you are speculating so much on other people diet, and making up theories
Edit:

Danny made a video on YT showing three or four of his meals and that’s what they were. I forgot the juice and cokes.

 

[R J]

Why does peat not look significantly younger than his age? Why does haidut not look younger? Why do they both have great energy output despite that? Why is the rp diet one among many if it doesn’t have drawbacks, given we are in the internet age?
Why do greenland sharks get so old despite extremely low metabolic rate?
Why do we not find significantly older people in tribes far from the environmental factors of civilization and eating fruit and animal protein exclusively?
Why is literally every extremely old person to have lived low or very low in bmi?

Georgi actually looks pretty good to me. He exhudes intelligent creative energy. You should trust me on my interpretation because as I said I have reverse autism. It’s a gift I’ve had for many years now.

 

[PxD]

Well, that escalated quickly.

What I wanted to point out when I made the original post was that Sinclair has recently buttoned on to the idea of caloric restriction/amino acid restriction for extending lifespan. This isn't really new knowledge, but Sinclair has contributed something to it by confirming the prior results via looking at the lab animals' DNA (Horvath clock test), and popularizing it.

My further point was that Peat knew this years (if not decades) ago already and furthermore he pointed out that it is not actually the caloric restriction that does the life-extension trick, but restriction of cysteine, methionine, and tryptophan. When you restrict calories, you restrict these amino acids automatically and the benefits of doing so outweigh whatever drawbacks there are to eating 1,500 calories a day. Peat's key insight is that you don't have to make the miserable tradeoff of starving yourself to live longer. You can have your calories and you can have your life extension by restricting specific amino acids (and PUFA, etc.) and increasing other aminos (e.g. glycine).

Sinclair is now rewalking steps that Peat walked many years ago. Judging by the number of view of Sinclair's presentations and interviews on YouTube, and his book sales, it looks like this is getting mainstream attention. I wonder if 10 years from now, Sinclair ends up completely rewalking Peat's path and starts preaching reduction of certain aminos, eating gelatin, etc.

Another outcome is that Sinclair stagnates and sticks to what he has now, and becomes a guru to a flock of near-starvation diet faddists for the next 20 years (I hope not).

 

[R J]

REMINDER:

-David Sinclair made $700 million for himself and Harvard after selling a resveratrol molecule to GSK, who did like one study and realized it was worthless and shelved it

—after scamming nearly a billon dollars like this, David had the audacity to go on YT and e-beg for crowdfunding for his NAD+ research

-David has Botox injections like some LA trophy wife

-David himself said he takes metformin and likes the fact it makes his stomach hurt so he doesn’t feel like eating. This is the rationale of a crazy person imho

-I’m pretty sure Niacinamide does all the good stuff NR does at pennies on the dollar

 

[Ableton]

Dig it. Good points, I'm resonating.

The bit about cooked meat/leaves reminds me of the Instincto Diet (aka Anopsology) developed by Guy Claude-Burger:

_Is anyone else currently coming out against cooking?

o Charges are coming up all over. In the United States, for instance, a cancerologist by the name of Ames devised a method intended to rate the effects of dietary carcinogens. He managed to assess that eating ordinary cooked food leads to an intake of carcinogens tantamount to smoking 40 cigarettes a day. If the food is grilled, which some believe is healthier, one can clock up to a hundred cigarettes a day!

...

Unfortunately, since it takes more like 24 or 48 years to kill you off with the slow relentlessness of arterial sclerosis, how could you possibly make the connection?​

its why I have almost completely eliminated heated fats from my diet. I dont think there is a problem with steaming food or cooking it in water. its heated fat, even saturated that is terrible. I always have an endocrinic reaction to it too (sebum, sometimes sweat). Heated fats are terrible, especially on extreme temperatures. Sat fats always have pufa content as well
Also, I just created this thread for people to discuss:
Hypothyroidism Is Naturally Induced Chemo Therapy. Every Metabolic Stressor Is A Carcinogenic

 

[cjm]

its why I have almost completely eliminated heated fats from my diet. I dont think there is a problem with steaming food or cooking it in water. its heated fat, even saturated that is terrible. I always have an endocrinic reaction to it too (sebum, sometimes sweat). Heated fats are terrible, especially on extreme temperatures. Sat fats always have pufa content as well
Also, I just created this thread for people to discuss:
Hypothyroidism Is Naturally Induced Chemo Therapy. Every Metabolic Stressor Is A Carcinogenic

Very interesting about the fats, can't say I've paid enough attention to notice a difference when they're heated. I believe Anopsology's main villain is advanced glycation end products (AGEs), though I'm not sure the Guy ever mentions them by name. AGEs are sugar/protein linkages methinks.

Glycemia, starch, and sugar in context

The bulk of the age-related tissue damage classified as “glycation end-products” (or “advanced glycation end-products,” AGE) is produced by decomposition of the polyunsaturated fats, rather than by sugars, and this would be minimized by the protective oxidation of glucose to carbon dioxide.​

Lipid peroxidation is a big deal when it comes to unsaturated, especially linoleic. I avoid the hell out of linoleic acid. Never come across evidence that saturated fats met the same fate, if you have any links.

Wait, so no pizza?! Melted cheese is too good to give up!

I need to synthesize my thoughts about the topic but I'll come back to your thread, or I'll see you on the forum somewhere.

 

[Kram]

You should clarify. Are you saying that often the repair job doesn't finish or leaves scars (which I would subscribe to) , or that there is stress/destruction inherent in the regeneration process? The former is prescriptive of higher metabolism to complete the job.

EDIT: You answered this already. It sounds like we're on the same page.

Here's a timely Haidut post that speaks against the "wear and tear" theory:

Low, not high, metabolism creates oxidative stress

From the study: "Some electrons are directly transferred to O2 to generate reactive oxygen species (ROS) in the ETC. The second part of this review discusses the sites of ROS generation in each ETC complex, including sites IF and IQ in complex I, site IIF in complex II and site IIIQo in complex III, and the physiological and pathological regulation of ROS. As signaling molecules, ROS play an important role in cell proliferation, hypoxia adaptation and cell fate determination, but excessive ROS can cause irreversible cell damage and even cell death. The occurrence and development of a number of diseases are closely related to ROS overproduction"

Haidut's comments: "it is low oxidative metabolism (OXPHOS), not high, that causes ROS generation. In other words, it is low OXPHOS that causes aging, not high."
​

This stuff is way over my head but most of Haidut's previous posts on ROS seem to indicate that high metabolism = high ROS, which is beneficial. This seems to contradict that...

 

[cjm]

This stuff is way over my head but most of Haidut's previous posts on ROS seem to indicate that high metabolism = high ROS, which is beneficial. This seems to contradict that...

Lol, now is when I confess I am confused about this, too.

I'm following along with Fire in a Bottle and dude there has a "ROS Theory of Obesity":

The ROS Theory of Obesity
The ROS theory says that energy balance is largely controlled by the interplay between ROS (Reactive Oxygen Species) produced in the mitochondria and hypothalamus and hormones like insulin and leptin. In this theory saturated fat – both from the diet and produced in the body from carbohydrate – acts as a molecular switch that by creating ROS in the mitochondria toggles the metabolism between running on glucose and running on fat. Saturated fat provides metabolic flexibility – the ability to tap into fat stores when available.

ROS, generated from saturated fat metabolism (oxidation), is the signal that prevents cells from switching from fat metabolism to glucose metabolism. They do this by creating a short term condition of physiological insulin resistance which prevents cells from responding to insulin – and therefore switching over to glucose burning – as long as the cells are still burning saturated fat.

You read that correctly. I am arguing that everything we think we know about obesity is exactly backwards. Instead of choosing unsaturated fats to avoid free radical formation which leads to insulin resistance we should be seeking out long chain saturated fats which cause free radical formation which leads to physiological insulin resistance.
​

Having some cognitive dissonance because I thought the whole point of saturated fat was to be a kind of antioxidant, but he's saying it promotes ROS, which is associated with low metabolism in the study.

 

[MitchMitchell]

God yeah, sticking to steamed / boiled foods is such a game changer. Specially for me as my skin is very sensitive. I can see right there on the spot what’s good and what isn’t.

Glad I’m not the only one noticing it.

Who’s that Ames doc? I’ll google them but any decent material should be shared here. Appreciated!

 

[CLASH]

Lol, now is when I confess I am confused about this, too.

I'm following along with Fire in a Bottle and dude there has a "ROS Theory of Obesity":

The ROS Theory of Obesity
The ROS theory says that energy balance is largely controlled by the interplay between ROS (Reactive Oxygen Species) produced in the mitochondria and hypothalamus and hormones like insulin and leptin. In this theory saturated fat – both from the diet and produced in the body from carbohydrate – acts as a molecular switch that by creating ROS in the mitochondria toggles the metabolism between running on glucose and running on fat. Saturated fat provides metabolic flexibility – the ability to tap into fat stores when available.

ROS, generated from saturated fat metabolism (oxidation), is the signal that prevents cells from switching from fat metabolism to glucose metabolism. They do this by creating a short term condition of physiological insulin resistance which prevents cells from responding to insulin – and therefore switching over to glucose burning – as long as the cells are still burning saturated fat.

You read that correctly. I am arguing that everything we think we know about obesity is exactly backwards. Instead of choosing unsaturated fats to avoid free radical formation which leads to insulin resistance we should be seeking out long chain saturated fats which cause free radical formation which leads to physiological insulin resistance.
​

Having some cognitive dissonance because I thought the whole point of saturated fat was to be a kind of antioxidant, but he's saying it promotes ROS, which is associated with low metabolism in the study.

His idea is specific to adipose cells, if I'm not mistaken. The adipose cells become insulin resistant from the saturated fat meaning less glucose uptake and fat synthesis. The implication is that other tissues, such as the neural tissues would be rerouted the glucose.

 

[Ableton]

God yeah, sticking to steamed / boiled foods is such a game changer. Specially for me as my skin is very sensitive. I can see right there on the spot what’s good and what isn’t.

Glad I’m not the only one noticing it.

Who’s that Ames doc? I’ll google them but any decent material should be shared here. Appreciated!

I Dont Tolerate Food X Anymore, I Can’t Eat Anything Anymore

 

[cjm]

His idea is specific to adipose cells, if I'm not mistaken. The adipose cells become insulin resistant from the saturated fat meaning less glucose uptake and fat synthesis. The implication is that other tissues, such as the neural tissues would be rerouted the glucose.

Ah, killer! Thanks for clarifying, man.

 

[DennisX]

WRT Time restricted feeding,, if a rodent doesn't get any food for 48 hrs it dies. So a rodents 16//8 or. 18/6 is not equivalent to a humans 16/8. All the time restricted rodent data is not directly applicable to humans.

 

[cjm]

God yeah, sticking to steamed / boiled foods is such a game changer. Specially for me as my skin is very sensitive. I can see right there on the spot what’s good and what isn’t.

Glad I’m not the only one noticing it.

Who’s that Ames doc? I’ll google them but any decent material should be shared here. Appreciated!

I posted a reply in Abelton's thread. When I did a forum search, I found a Ray quote that made me stop and think. I can't get my head around "cooking = bad" -- cooking increases digestibility and palatability, and reduces parasites, and the body has ways of dealing with the carcinogenic compounds.

Vegetables, etc.—Who Defines Food?

"Many types of phytochemicals are mutagenic, and some of those are carcinogenic. Bruce Ames, at the University of California, devised a method of screening for mutagens, using bacteria. One of his graduate students using the technique found that the flame retardants in children's pajamas and bedding were powerful mutagens, and were probably causing cancer. That event made Ames a celebrity, and in the 1980s he went on a lecture tour supported by the American Cancer Society. His lectures reflected the doctrine of the A.C.S., that industrial chemicals aren't responsible for cancer, but that individual actions, such as smoking or dietary choices, are the main causes of cancer. He used a fraudulently "age adjusted" graph of cancer mortality, that falsely showed that mortality from all types of cancer except lung cancer had leveled off after the A.C.S. came into existence. He described tests in which he had compared DDT to extracts of food herbs, and found DDT to be less mutagenic than several of the most commonly used flavoring herbs. His message, which was eagerly received by his audience of chemistry and biology professors, was that we should not worry about environmental pollution, because it's not as harmful as the things that we do to ourselves. He said that if everyone would eat more unsaturated vegetable oil, and didn't smoke, they wouldn't have anything to worry about.

For me, the significance of his experiment was that plants contain natural pesticides that should be taken more seriously, without taking industrial toxins less seriously."
​

Here are the three Ames studies (plus another on cytotoxicity of herbs) cited in the article:

Med Oncol Tumor Pharmacother 1990;7(2-3):69-85. Dietary carcinogens, environmental pollution, and cancer: some misconceptions. Ames BN, Gold LS Division of Biochemistry and Molecular Biology, University of California, Berkeley 94720. Various misconceptions about dietary carcinogens, pesticide residues, and cancer causation are discussed. The pesticides in our diet are 99.99% natural, since plants make an enormous variety of toxins against fungi, insects, and animal predators. Although only 50 of these natural pesticides have been tested in animal cancer tests, about half of them are carcinogens. About half of all chemicals tested in animal cancer tests are positive. The proportion of natural pesticides positive in animal tests of clastogenicity is also the same as for synthetic chemicals. It is argued that testing chemicals in animals at the maximum tolerated dose primarily measures chronic cell proliferation, a threshold process. Cell proliferation is mutagenic in several ways, including inducing mitotic recombination, and therefore chronic induction of cell proliferation is a risk factor for cancer.

Proc Natl Acad Sci U S A 1980 Aug;77(8):4961-5. Fecalase: a model for activation of dietary glycosides to mutagens by intestinal flora. Tamura G, Gold C, Ferro-Luzzi A, Ames BN Many substances in the plant kingdom and in man's diet occur as glycosides. Recent studies have indicated that many glycosides that are not mutagenic in tests such as the Salmonella test become mutagenic upon hydrolysis of the glycosidic linkages. The Salmonella test utilizes a liver homogenate to approximate mammalian metabolism but does not provide a source of the enzymes present in intestinal bacterial flora that hydrolyze the wide variety of glycosides present in nature. We describe a stable cell-free extract of human feces, fecalase, which is shown to contain various glycosidases that allow the in vitro activation of many natural glycosides to mutagens in the Salmonella/liver homogenate test. Many beverages, such as red wine (but apparently not white wine) and tea, contain glycosides of the mutagne quercetin. Red wine, red grape juice, and tea were mutagenic in the test when fecalase was added, and red wine contained considerable direct mutagenic activity in the absence of fecalase. The implications of quercetin mutagenicity and carcinogenicity are discussed.

Nutr Cancer 1988;11(4):251-7. Cytotoxicity of extracts of spices to cultured cells. Unnikrishnan MC, Kuttan R Amala Cancer Research Centre, Kerala, India. The cytotoxicity of the extracts from eight different spices used in the Indian diet was determined using Dalton's lymphoma ascites tumor cells and human lymphocytes in vitro and Chinese Hamster Ovary cells and Vero cells in tissue culture. Alcoholic extracts of the spices were found to be more cytotoxic to these cells than their aqueous extracts. Alcoholic extracts of several spices inhibited cell growth at concentrations of 0.2-1 mg/ml in vitro and 0.12-0.3 mg/ml in tissue culture. Ginger, pippali (native to India; also called dried catkins), pepper, and garlic showed the highest activity followed by asafetida, mustard, and horse-gram (native to India). These extracts also inhibited the thymidine uptake into DNA.

J Toxicol Sci 1984 Feb;9(1):77-86. [Mutagenicity and cytotoxicity tests of garlic]. [Article in Japanese] Yoshida S, Hirao Y, Nakagawa S Mutagenicity and cytotoxicity of fresh juice and alcohol extract from garlic were studied by Ames' test, Rec assay, Micronucleus test and the check of the influence to HEp 2 and chinese hamster embryo (CHE) primary cultured cells. No evidence of mutagenicity of these samples were observed in Ames' test and Rec assay, while there was dose dependent increase of micronucleated cells and polychromatocytes on the bone marrow cells of mice and chinese hamsters treated with garlic juice. There were severe damages, e.g. growth inhibition and morphological changes of both cultured cells due to garlic juice, but no or slightly cytotoxic signs were observed even in high concentration of garlic extract. A higher sensitivity to the cytotoxic effects of garlic was seen by the present findings with CHE primary cells than HEp 2 cell line.​