speaker's introduction
Internationally renowned expert on the biology of aging. He was at the International Conference on Aging Medicine at Rio de Janiero, and the first European Conference on Longevity Medicine and many more. He is the author of The Rosedale Diet: Insulin and its metabolic effects. He will be speaking to us this morning on the detrimental effects of too much protein.
RONALD ROSEDALE
We might give a different view on protein intake and nutrition and actually health in general. First, you hear a lot about paleolithic nutrition, the idea being that ancient man can tell us how to be healthy. That we need to go back to our ancient roots and eat like they did, and then we'll be healthy. But you have to go back even further and understand what Nature is after. And there are two prime prerogatives of all life, since the beginning of life. And they both involve making more life.
TWO PRIME PREROGATIVES
What do you do to reproduce? You have to eat.
You have to eat and reproduce. It's all life does, and we evolved with those dictums.
How do you make more life? Reproduce.
We can't use Paleolithic Man. We evolved with a diet to not allow a man to live a long healthy life.
Nature does not care about us living a long healthy life, or any life, for that matter. Nature wants "Life" to live.
It's like, you don't care if there's a little cell on your hand that dies, as long as the whole remains. Nature doesn't care if you or I dies, or if all mankind dies. Nature wants life to live.
The diet that ancient man grew up with was to maximize reproductive sense. Not necessarily the life of each individual.
Nature does not care about us living a long healthy life, or any life, for that matter. Nature wants "Life" to live.
It's like, you don't care if there's a little cell on your hand that dies, as long as the whole remains. Nature doesn't care if you or I dies, or if all mankind dies. Nature wants life to live.
The diet that ancient man grew up with was to maximize reproductive sense. Not necessarily the life of each individual.
ENERGY STORES
We do know, there is a powerful connection between energy stores, reproduction and longevity. Certainly, we know that it takes a lot of energy to make babies. And if there was not a lot of energy around, Nature would put off reproduction, and it is that trick that we want to use. It puts off reproduction by allowing the organism to live longer. It appears that all organisms have genetic mechanisms to delay aging, to delay dying so that the organism can reproduce at a future more opportune time. And generally this is genetically controlled, and it's controlled by the availability of nutrients, whether it's good to reproduce now or put off reproduction into the future.
Because of this, we know now that there are nutrient sensors that tell the body and tell the genetics how much nutrition is available right now, and it is a liaison between nutrient stores and genetic expression that determines whether the body will move toward reproduction or maintenance and repair. This is on an organism level and on a cellular level. On a cellular level, increasing reproduction might not be such a good thing because when you push growth and reproduction too far, you stimulate cancer.
Because of this, we know now that there are nutrient sensors that tell the body and tell the genetics how much nutrition is available right now, and it is a liaison between nutrient stores and genetic expression that determines whether the body will move toward reproduction or maintenance and repair. This is on an organism level and on a cellular level. On a cellular level, increasing reproduction might not be such a good thing because when you push growth and reproduction too far, you stimulate cancer.
LONGEVITY
Caloric restriction, metabolism, IGF and insulin are integrated into this longevity pathway, and this pathway appears to be conserved through all of evolution.
It's found in yeast and flies and worms. Everything down to yeast. Not bacteria. Bacteria has a different definition of life. In fact, it never dies. It just keeps reproducing. So you can't throw bacteria in there. But yeast, flies, worms, rodents, primates, and certainly humans, it appears. Since the discovery of insulin, most studies have focused on the role of insulin in the metabolism of glucose, however a failure of insulin signaling is certainly associated with a shorter lifespan. What we're seeing over the last decade is a central role of insulin signaling in lifespan. The discoveries indicate that aging is a programmed and well controlled process regulated by the same pathways that affect growth, metabolism and lifespan. It is an evolutionarily conserved process, so you can extrapolate, it appears, to humans, since it appears ubiquitous.
It's found in yeast and flies and worms. Everything down to yeast. Not bacteria. Bacteria has a different definition of life. In fact, it never dies. It just keeps reproducing. So you can't throw bacteria in there. But yeast, flies, worms, rodents, primates, and certainly humans, it appears. Since the discovery of insulin, most studies have focused on the role of insulin in the metabolism of glucose, however a failure of insulin signaling is certainly associated with a shorter lifespan. What we're seeing over the last decade is a central role of insulin signaling in lifespan. The discoveries indicate that aging is a programmed and well controlled process regulated by the same pathways that affect growth, metabolism and lifespan. It is an evolutionarily conserved process, so you can extrapolate, it appears, to humans, since it appears ubiquitous.
CALORIE RESTRICTION
Calorie restriction also appears to ubiquitously extend lifespan in laboratory animals, and so far, it appears to extend lifespan in humans, too. It extends lifespan in yeast, flies, fish, worms, mice, rats, monkeys, and perhaps humans. Some common, consistent effects of caloric restriction include lower fat mass, particularly visceral fat–remember that–lower circulating insulin and IGF concentrations, increased insulin sensitivity, lower body temperature. Flowers live longer if you keep them cooler. It appears to be a universal truth. Lower fat free mass. Lower sedentary energy expenditure. Decreased levels of thyroid hormone and decreased oxidative stress. Reduced metabolism and therefore free radical production is another possible explanation. And there Other effects such as lower body temperature, decreased insulin, decreased IGF, decreased sympathetic nervous system activity, altered gene expression have all been suggested as mechanisms that explain the extended lifespan associated with calorie restriction.
There's also a connection between calorie restriction and chromatin structure. Genes are wrapped around chromatin, and their expression is often dictated by how well they're wrapped. Basically, you uncover the genes to read them. Genetic expression is really the importance of genetics. It's not the genes you have. Every cell in your body other than your sperm and eggs have the same genes. What makes a heart cell a heart cell and a kidney cell a kidney cell depends on which genes are read. That depends on chromatin structure and other molecular mechanisms such as methylation and acetylation and things like that.
This is talking about an important part of genetic expression dictated by a gene called SIR-2 which in the humans, the homologue is SIRT-1, and research at MIT and Harvard has looked and determined this pathway is NAD and NAHD dependent, meaning energy stores, and when SIRT-1 in humans and SIRT 2 in so called lower forms of animals goes up, animals tend to live longer, and it appears it does this by turning off detrimental pathways that can accelerate aging and turns on maintenance and repair pathways that extend lifespan, and at least partially, you can up-regulate SIRT expression and therefore, by suggestion, lifespan, by amino acid restriction.
Interestingly also, SIRT-1 protein binds to and represses genes controlled by the fat regulator PPR. Where have you heard that before? That's Avandia, Actos. The first one was Rezulun but they had to take it off the market because it killed too many people. They still kept the other drugs on the market. These are supposedly insulin sensitizers. They are NOT insulin sensitizers. That's just marketing hype. These PPR agonist drugs such as Actos and Avandia actually work by increasing fat mass. They multiply fat cells. They give you a bigger dumping ground to put sugar. So yes, it lowers blood sugar. Only because you turn it into fat. But is that a healthy thing to do?
There's also a connection between calorie restriction and chromatin structure. Genes are wrapped around chromatin, and their expression is often dictated by how well they're wrapped. Basically, you uncover the genes to read them. Genetic expression is really the importance of genetics. It's not the genes you have. Every cell in your body other than your sperm and eggs have the same genes. What makes a heart cell a heart cell and a kidney cell a kidney cell depends on which genes are read. That depends on chromatin structure and other molecular mechanisms such as methylation and acetylation and things like that.
This is talking about an important part of genetic expression dictated by a gene called SIR-2 which in the humans, the homologue is SIRT-1, and research at MIT and Harvard has looked and determined this pathway is NAD and NAHD dependent, meaning energy stores, and when SIRT-1 in humans and SIRT 2 in so called lower forms of animals goes up, animals tend to live longer, and it appears it does this by turning off detrimental pathways that can accelerate aging and turns on maintenance and repair pathways that extend lifespan, and at least partially, you can up-regulate SIRT expression and therefore, by suggestion, lifespan, by amino acid restriction.
Interestingly also, SIRT-1 protein binds to and represses genes controlled by the fat regulator PPR. Where have you heard that before? That's Avandia, Actos. The first one was Rezulun but they had to take it off the market because it killed too many people. They still kept the other drugs on the market. These are supposedly insulin sensitizers. They are NOT insulin sensitizers. That's just marketing hype. These PPR agonist drugs such as Actos and Avandia actually work by increasing fat mass. They multiply fat cells. They give you a bigger dumping ground to put sugar. So yes, it lowers blood sugar. Only because you turn it into fat. But is that a healthy thing to do?
LIFESPAN
Insulin/IGF represents a family of growth factors that regulate metabolism, growth, cell differentiation and survival. It links insulin action to the map-kinase pathway of cell division. Here's a very important gene, one of the first genes that was discovered that can extend lifespan is DAF-2 discovered by Cynthia Kenyon at University of California in San Francisco that amazed everyone. They didn't know at the time what it did, but they did know that DAF-2 mutants can live four times longer. They found a moderate decrease in insulin IGF-1 signaling has been shown to extend lifespan in mice. It's associated with lower levels of insulin, and it's similar to the improved insulin sensitivity that you see in caloric restriction.
In mouse models, decreased food intake can extend lifespan, and there's a special role for insulin signaling in fat in the longevity process. Reduced fat tends to lower insulin and protects you from diabetes. They found, by testing various tissues that if you just reduce fat levels, and you enhance insulin sensitivity while reducing fat levels in fat tissue, you extend lifespan. So it doesn't have to be all over. Fat tissue is a particularly important part of this process. Just a moderate decrease in insulin and IGF signaling has been shown to extend lifespan in mice. This was done by a friend of mine, Andre Bartke and he's done a lot of studies in mice and shows that if you down regulate insulin and IGF signaling, and you increase insulin sensitivity, you can increase lifespan in mice. A couple of years ago he won the Methusula award. It's given to the researcher who can extend the life of a mouse the longest. I think he's extended lifespan about six years now in mice. The normal lifespan is two years. What they're doing in these laboratories is amazing. They're tripling lifespan. They're doing it by the same pathways of genetics that we have in humans. They're going into the genetics of it, which we can't quite do in humans yet. The genetics are altered by nutritional stores and nutrient sensors. We do have a way to dig into these genes. Maybe not with pliers yet, but by what we put in our mouths.
Centenarians, people who live to be 100 or older, have lower insulin and IGF levels. One of the nice ways to study aging in humans is on centenarians. Centenarians, they've been showing now for quite a few years that there are differences among centenarians. They eat different diets, they smoke and have different personalities. There are not a lot of similarities between centenarians. But they universally have lower IGF, lower insulin, lower temperature and lower thyroid levels. Those go together.
Conclusions: Strong similarities exist between insulin and IGF systems. Maybe linked to oxidative stress, lifespan. It suggests that the Insulin-IGF system arose early in evolution and it is an essential component of anti-aging systems which is conserved from yeast to humans.
Now let's look at a slightly different view on how insulin works. The typical thinking is that the most important organs that will determine whether a person will become diabetic is how insulin sensitive the muscles, fat and liver are. But that doesn't seem to be the case. In mice, they turned on and off genes of insulin receptors in different tissues of the body. They determined that the two organs most important by far in determining whether an organism will be diabetic or not are whether it has insulin sensitivity in the brain and liver. Two big keys in determining health and diabetes. These researchers say that we've overestimated how important insulin is in muscle and fat and underestimated its importance in other tissues.
In mouse models, decreased food intake can extend lifespan, and there's a special role for insulin signaling in fat in the longevity process. Reduced fat tends to lower insulin and protects you from diabetes. They found, by testing various tissues that if you just reduce fat levels, and you enhance insulin sensitivity while reducing fat levels in fat tissue, you extend lifespan. So it doesn't have to be all over. Fat tissue is a particularly important part of this process. Just a moderate decrease in insulin and IGF signaling has been shown to extend lifespan in mice. This was done by a friend of mine, Andre Bartke and he's done a lot of studies in mice and shows that if you down regulate insulin and IGF signaling, and you increase insulin sensitivity, you can increase lifespan in mice. A couple of years ago he won the Methusula award. It's given to the researcher who can extend the life of a mouse the longest. I think he's extended lifespan about six years now in mice. The normal lifespan is two years. What they're doing in these laboratories is amazing. They're tripling lifespan. They're doing it by the same pathways of genetics that we have in humans. They're going into the genetics of it, which we can't quite do in humans yet. The genetics are altered by nutritional stores and nutrient sensors. We do have a way to dig into these genes. Maybe not with pliers yet, but by what we put in our mouths.
Centenarians, people who live to be 100 or older, have lower insulin and IGF levels. One of the nice ways to study aging in humans is on centenarians. Centenarians, they've been showing now for quite a few years that there are differences among centenarians. They eat different diets, they smoke and have different personalities. There are not a lot of similarities between centenarians. But they universally have lower IGF, lower insulin, lower temperature and lower thyroid levels. Those go together.
Conclusions: Strong similarities exist between insulin and IGF systems. Maybe linked to oxidative stress, lifespan. It suggests that the Insulin-IGF system arose early in evolution and it is an essential component of anti-aging systems which is conserved from yeast to humans.
Now let's look at a slightly different view on how insulin works. The typical thinking is that the most important organs that will determine whether a person will become diabetic is how insulin sensitive the muscles, fat and liver are. But that doesn't seem to be the case. In mice, they turned on and off genes of insulin receptors in different tissues of the body. They determined that the two organs most important by far in determining whether an organism will be diabetic or not are whether it has insulin sensitivity in the brain and liver. Two big keys in determining health and diabetes. These researchers say that we've overestimated how important insulin is in muscle and fat and underestimated its importance in other tissues.
LEPTIN REVIEW
Are people here familiar, cause I'm skipping over and assuming people are familiar with what leptin usually does.
Here's a very brief review. Leptin was discovered about ten years ago. Produced by fat. It's supposed to tell your hypothalamus how much fat you've got and whether to produce more fat. And whether you should keep eating to produce more fat or get rid of some excess. In our evolutionary history, it was good to store some fat. All of our ancestors encountered a famine. You needed to have a good energy source. Fat's a good, efficient energy source, but it wasn't good to be too fat, because if you were too fat, you were going to end up as a meal for another organism. Because if you are running from a lion in a group of people, which one is it going to catch? If you got too fat, the lion catches you, because you can't run up a tree. And those genes would have been eliminated from the gene pool. Leptin tells the brain how much fat there is, and whether you should get more fat or you shouldn't..
Which means, leptin controls whether or not you're hungry.
It, leptin, knows people are only going to do what they feel like doing. The only way to get people to lose weight is, which means to lose fat, is to get people to not eat too much. That means they can't be hungry. Trying to not eat in the face of hunger is an impoosibility, it's bound to fail. That's why you see this yo yo dieting. If you're hungry, ultimately, you're going to eat. It's like holding onto a cliff. You look down two miles, and you know if you let go, you're going to die. Gravity is unrelenting. So is hunger.
Here's a very brief review. Leptin was discovered about ten years ago. Produced by fat. It's supposed to tell your hypothalamus how much fat you've got and whether to produce more fat. And whether you should keep eating to produce more fat or get rid of some excess. In our evolutionary history, it was good to store some fat. All of our ancestors encountered a famine. You needed to have a good energy source. Fat's a good, efficient energy source, but it wasn't good to be too fat, because if you were too fat, you were going to end up as a meal for another organism. Because if you are running from a lion in a group of people, which one is it going to catch? If you got too fat, the lion catches you, because you can't run up a tree. And those genes would have been eliminated from the gene pool. Leptin tells the brain how much fat there is, and whether you should get more fat or you shouldn't..
Which means, leptin controls whether or not you're hungry.
It, leptin, knows people are only going to do what they feel like doing. The only way to get people to lose weight is, which means to lose fat, is to get people to not eat too much. That means they can't be hungry. Trying to not eat in the face of hunger is an impoosibility, it's bound to fail. That's why you see this yo yo dieting. If you're hungry, ultimately, you're going to eat. It's like holding onto a cliff. You look down two miles, and you know if you let go, you're going to die. Gravity is unrelenting. So is hunger.
LEPTIN AS BRAIN REGULATOR
Here's a study that raised eyebrows. After you're born, everybody thought your brain had fixed neuron connections and they showed that leptin actually changes nerve endings in the brain to do its bidding. If it wants to make you hungry, it doesn't just do it by neurotransmitters. The "fat brain" actually changes the anatomy of the brain, and leptin is a crucial regulator, including synaptic plasticity and axon guidance within the hypothalamus. Links between nutrition and adipocyte driven instructions from leptin . . . leptin makes you hungry, it actually changes the anatomy of the brain. It's talking about the fat brain accesses a new dimension in the journal science. Axon guidance within the hypothalamus.
Very important clinical implications. Leptin controls not only how fat your are, but where you're fat. For a long time we've heard about the apple shape versus the pear shape. The apple shape is associated with much more detrimental physiological processes. The pear shape might look ugly, but it's not particularly unhealthy. It's visceral fat versus subcutaneous fat. Visceral fat is a totally different organ than subcutaneous fat. It produces different hormones. Visceral fat is really bad for you. If you've got visceral fat, it's because of leptin resistance.
Islets within the pancreas can get fat. We think of ourselves as a single individual. We have to think that we're 10 trillion cells, and cells can get too fat. Just as getting fat is not good for us, being fat is not good for cells. Beta cells in the pancreas can get fat, and when they do, they can't produce insulin properly. That's another way that leptin controls glucose and determines whether you're a diabetic or not. Whether the cells are getting fat or not is being proposed to be caused by leptin. We propose the signal is leptin and its function is to create for adipocytes a monopoly on fat storage, to maintain a constancy of intracellular triglycerides and adipocytes. So when things are working properly, you store fat in fat cells. When the signals or getting messed up, you start storing fat in other places,and it's when you start storing fats in other places you get really unhealthy.
Bears get really fat prior to hibernating. But bears don't get heart disease, because their fat is stored almost all in subcutaneous fat, not in visceral tissues. So being fat doesn't make you sick. Being fat in the viscera makes you sick. Being fat in places other than the subcutaneous tissue makes you sick. And that's determined by leptin.
Very important clinical implications. Leptin controls not only how fat your are, but where you're fat. For a long time we've heard about the apple shape versus the pear shape. The apple shape is associated with much more detrimental physiological processes. The pear shape might look ugly, but it's not particularly unhealthy. It's visceral fat versus subcutaneous fat. Visceral fat is a totally different organ than subcutaneous fat. It produces different hormones. Visceral fat is really bad for you. If you've got visceral fat, it's because of leptin resistance.
Islets within the pancreas can get fat. We think of ourselves as a single individual. We have to think that we're 10 trillion cells, and cells can get too fat. Just as getting fat is not good for us, being fat is not good for cells. Beta cells in the pancreas can get fat, and when they do, they can't produce insulin properly. That's another way that leptin controls glucose and determines whether you're a diabetic or not. Whether the cells are getting fat or not is being proposed to be caused by leptin. We propose the signal is leptin and its function is to create for adipocytes a monopoly on fat storage, to maintain a constancy of intracellular triglycerides and adipocytes. So when things are working properly, you store fat in fat cells. When the signals or getting messed up, you start storing fat in other places,and it's when you start storing fats in other places you get really unhealthy.
Bears get really fat prior to hibernating. But bears don't get heart disease, because their fat is stored almost all in subcutaneous fat, not in visceral tissues. So being fat doesn't make you sick. Being fat in the viscera makes you sick. Being fat in places other than the subcutaneous tissue makes you sick. And that's determined by leptin.
LEPTIN REGULATING THE LIVER
The other tissue that's very importantly regulated by leptin is the liver, via the vagal nerve from the hypothalamus, but it also determines how fat the liver is, and a few studies here talk about non-alcoholic fatty liver disease. Fatty liver is grossly under-diagnosed. It affects at least two thirds of obese people, perhaps more, and also some people who are not obese. It almost totally parallels the incidence of the so-called metabolic syndrome, and many people believe that metabolic syndrome is actually caused by fatty liver. Which is determined by leptin.
Fatty liver disease is strongly associated with diabetes. High cholesterol. Hypertension. The process starts when there's so much dietary fat in the blood it can no longer be stored in normal places such as fat cells.
Leptin treatment decreased visceral fat specifically, supporting the role of leptin in determining fat distribution. That's a very important role of leptin. Determining not only whether you're fat, but where you're fat. Perhaps more important.
We're talking about cardiovascular disease now. There's a link between insulin action and cardiovascular disease. And Insulin resistance in the development of diabetes can be reduced by preventing the age-dependant accumulation of visceral fat.
When you do liposuction, it doesn't really help health by taking out subcutaneous fat. It didn't really help diabetics. But if they took out the omentum in mice, they could totally reverse diabetes in mice. So they're starting to do this in humans, at Vanderbilt. Leptin activity increases aromatase activity, in visceral fat (not subcutaneous), which converts testosterone and estrogen, which is why you see all these overweight men with breasts. That's because of an increase in aromatase, and that's not good because it's also a powerful increaser of cancer, particularly prostate cancer.
Fatty liver disease is strongly associated with diabetes. High cholesterol. Hypertension. The process starts when there's so much dietary fat in the blood it can no longer be stored in normal places such as fat cells.
Leptin treatment decreased visceral fat specifically, supporting the role of leptin in determining fat distribution. That's a very important role of leptin. Determining not only whether you're fat, but where you're fat. Perhaps more important.
We're talking about cardiovascular disease now. There's a link between insulin action and cardiovascular disease. And Insulin resistance in the development of diabetes can be reduced by preventing the age-dependant accumulation of visceral fat.
When you do liposuction, it doesn't really help health by taking out subcutaneous fat. It didn't really help diabetics. But if they took out the omentum in mice, they could totally reverse diabetes in mice. So they're starting to do this in humans, at Vanderbilt. Leptin activity increases aromatase activity, in visceral fat (not subcutaneous), which converts testosterone and estrogen, which is why you see all these overweight men with breasts. That's because of an increase in aromatase, and that's not good because it's also a powerful increaser of cancer, particularly prostate cancer.
LEPTIN IS PRO-INFLAMMATORY
Some of this has to do with how it promotes hypoandrogenicity. Leptin is also a powerful pro-inflammatory agent. You've heard of the link between chronic inflammation and cardiovascular disease. Leptin is itself an inflammatory cytokine. But it also dictates the production of interleukins and TNF alfa, Which are pro-inflammatory agents linked to heart disease and diabetes.
Leptin is a novel independent risk factor for coronary heart disease. Leptin enhances the calcification of vascular cells. This was new to people. Leptin also helps control osteoporosis. It helps control where you put calcium. We think of osteoporosis, and women are being given the dictum to take a bunch of calcium. As if osteroporosis is caused by a lack of calcium. That is ridiculous.
How can one hormone make a difference in all these different things? It has to do with leptin's ability to control the rate of aging. Aging, or the lack of it, is determined by proper communication. When that communication goes awry, all kinds of things go wrong.
Leptin is a novel independent risk factor for coronary heart disease. Leptin enhances the calcification of vascular cells. This was new to people. Leptin also helps control osteoporosis. It helps control where you put calcium. We think of osteoporosis, and women are being given the dictum to take a bunch of calcium. As if osteroporosis is caused by a lack of calcium. That is ridiculous.
How can one hormone make a difference in all these different things? It has to do with leptin's ability to control the rate of aging. Aging, or the lack of it, is determined by proper communication. When that communication goes awry, all kinds of things go wrong.
LEPTIN AND BONES
Leptin controls osteoblastic activity in bones and vascular cells. High leptin inhibits bone formation via the hypothalmus. And the arterial wall may be an inportant target for leptin action. All the treatment for osteoporosis has to do with osteoclastic activity. Osteoclasts break down bone. They want to prevent the breakdown of bone. The drug treatments don't make new bones.
But bone strength is determined by the protein content, not the calcium content of bone. It's the flexibility of bone, which has nothing to do with bone density. It's the protein content of bones. You want to have protein, you need protein, but you want it in the right places, and you want it in the right amount. High leptin levels are a potent inhibitor of bone formation.
Life is not in the parts. We're all made of the same stuff. it's what you, or more accurately, your hormones, do with the parts, that will will determine whether you're healthy or not. That's really the way to think.
By changing leptin sensitivity, the Hypothalamic set point can be reversed. In regards to leptin levels, there's a Possible role of protein.
But bone strength is determined by the protein content, not the calcium content of bone. It's the flexibility of bone, which has nothing to do with bone density. It's the protein content of bones. You want to have protein, you need protein, but you want it in the right places, and you want it in the right amount. High leptin levels are a potent inhibitor of bone formation.
Life is not in the parts. We're all made of the same stuff. it's what you, or more accurately, your hormones, do with the parts, that will will determine whether you're healthy or not. That's really the way to think.
By changing leptin sensitivity, the Hypothalamic set point can be reversed. In regards to leptin levels, there's a Possible role of protein.
LEPTIN AND CALORIC RESTRICTION
Here, they're showing that a fall in leptin is one of things that mediates dietary restriction. If leptin doesn't fall, you're not going to live longer. In normal men, a fall in leptin in fasting may be both a necessary and sufficient physiological adaptation of these axes, which has to do with hypthalaumus, pituitary, gonads, IGF, thyroid. You have to drop leptin, or dietary restriction is not going to help.
Dietary restriction explained from an evolutionary viewpoint is an adaptive response by the neuroendocrine and metabolic response systems to maximize survival during times of food shortage. Adipose tissue is recognized as an endocrine organ, and leptin secreted by the adipocytes seems to be an especially important factor for the adaptive response to fasting and neuroendocrine response under caloric restriction.
The one known way to extend lifespan of every species studied since 1933 has been to reduce calories. Since that time, the emphasis has been to figure out why. Ten years ago, they discovered a gene that can control aging, Age-1 gene, discoered by Tom Johnson at the university of Colorado, and Cynthia Kenyon with DAF-2 expanded on this. These all link to nutrient sensors and it all links into a pathway that governs maintenance and repair or growth. They're all linked to nutrient receptors, and it appears that in mammals, leptin plays a key role, and those animals that use fat as a prime energy store, leptin plays a key role in the aging process.
Prior to leptin, and it appears that they're cousins, it was Insulin and IGF. Insulin and IGF in ancient organisms, insulin and Insulin like Growth factor were the same. Over time they evolved to have separate duties. Now insulin is more metabolic, and IGF is more anabolic.
Dietary restriction explained from an evolutionary viewpoint is an adaptive response by the neuroendocrine and metabolic response systems to maximize survival during times of food shortage. Adipose tissue is recognized as an endocrine organ, and leptin secreted by the adipocytes seems to be an especially important factor for the adaptive response to fasting and neuroendocrine response under caloric restriction.
The one known way to extend lifespan of every species studied since 1933 has been to reduce calories. Since that time, the emphasis has been to figure out why. Ten years ago, they discovered a gene that can control aging, Age-1 gene, discoered by Tom Johnson at the university of Colorado, and Cynthia Kenyon with DAF-2 expanded on this. These all link to nutrient sensors and it all links into a pathway that governs maintenance and repair or growth. They're all linked to nutrient receptors, and it appears that in mammals, leptin plays a key role, and those animals that use fat as a prime energy store, leptin plays a key role in the aging process.
Prior to leptin, and it appears that they're cousins, it was Insulin and IGF. Insulin and IGF in ancient organisms, insulin and Insulin like Growth factor were the same. Over time they evolved to have separate duties. Now insulin is more metabolic, and IGF is more anabolic.
LEPTIN AND LONGEVITY
Here again, talking about the importance of fat tissue in longevity. Leptin controls whether you're satiated or not. It also has to do with life extension. With PPAR alpha. Not PPAR gamma. PPAR gamma is what people are taking drugs for. PPAR gamma accelerates life and reduces lifespon. PPR Alpha enhances lifespan. Exactly the opposite. Leptin modulates this through the PPR system because PPR gamma influences a lot of what happens in fat.
Failure of leptin suggests leptin plays a major role in dietary restriction. There's a link between leptin concentration, with higher levels linked to telemere shortening, which is another theory for aging, that shorter telomeres reduces lifespan, and telomere shortening is controlled by leptin. Waist-to-hip ratio correlates with leptin levels. Centenarians have lower waist to hip ratio. Longer lifespan was predicted by lower levels of leptin. Here, they're showing that a bunch of amino acids stimulated leptin production.
Failure of leptin suggests leptin plays a major role in dietary restriction. There's a link between leptin concentration, with higher levels linked to telemere shortening, which is another theory for aging, that shorter telomeres reduces lifespan, and telomere shortening is controlled by leptin. Waist-to-hip ratio correlates with leptin levels. Centenarians have lower waist to hip ratio. Longer lifespan was predicted by lower levels of leptin. Here, they're showing that a bunch of amino acids stimulated leptin production.
LEPTIN AND FAT
In membrane composition, insulin and leptin regulate the types of fat found in membranes.
Talking about IGF again and membranes, that omega three fatty acids improve leptin sensitivity.
This is a study that hasn't been published yet, that is a collaboration between myself and Eric Westman and John Konhilas. What we're showing is that a high fat, adequate protein, low carbohydrate diet with nutritional supplements in an outpatient setting, resulted correlates of aging. There were reductions in body weight, triglycerides, insulin, glucose, leptin, free T3 The same things you see with caloric restriction. But we were not restricting calories. The reduction in insulin and leptin levels was strongly correlated with reduction in weight, but the reduction in leptin levels was far greater than the initial weight loss. In other words, leptin is not dictated by how fat you are. It's dictated by what you eat. Sugar increases leptin output, and amino acids increase leptin output.
Talking about IGF again and membranes, that omega three fatty acids improve leptin sensitivity.
This is a study that hasn't been published yet, that is a collaboration between myself and Eric Westman and John Konhilas. What we're showing is that a high fat, adequate protein, low carbohydrate diet with nutritional supplements in an outpatient setting, resulted correlates of aging. There were reductions in body weight, triglycerides, insulin, glucose, leptin, free T3 The same things you see with caloric restriction. But we were not restricting calories. The reduction in insulin and leptin levels was strongly correlated with reduction in weight, but the reduction in leptin levels was far greater than the initial weight loss. In other words, leptin is not dictated by how fat you are. It's dictated by what you eat. Sugar increases leptin output, and amino acids increase leptin output.
FAT AND LIFESPAN
You don't have to have any sugar, but you have to have some protein. But you don't want too much. Too much protein raises leptin and accelerates aging.
Your brain is a servant of your fat, your brain is what fat uses to do its bidding, and your fat's bidding will determine your lifespan.
Your brain is a servant of your fat, your brain is what fat uses to do its bidding, and your fat's bidding will determine your lifespan.