Aging. Is it a Treatable Disease?

1. Exercise and Muscle Maintenance

– Aerobic exercise increases NAD levels and Sirtuin gene expression

– Maintaining muscle mass is crucial for hormone regulation, especially testosterone

– Regular exercise can help maintain youthful hormone levels even in advanced age

2. Fasting and Caloric Restriction

– Intermittent fasting activates longevity genes and cellular repair mechanisms

– Constant feeding may prevent activation of protective mechanisms

– Periods of hunger can be beneficial for longevity and cellular health

3. Cellular Biology and Aging

– Sirtuins (a group of seven proteins) play crucial roles in aging regulation

– NAD levels are important for cellular health and aging prevention

– Obesity and excess fat tissue can accelerate aging through increased senescent cells

4. Temperature Regulation

– Mild cold exposure may help with metabolic health

– The “metabolic winter hypothesis” suggests humans evolved to handle periods of cold and hunger

– Thermoregulation challenges may help with energy expenditure and metabolism

5. Body’s Regenerative Capabilities

– The human body has significant healing and regenerative potential

– Age-related decline may not be as inevitable as previously thought

– Epigenetic modifications can influence aging and cellular function

Delving into the Science of Age Reversal: A Review of Dr. Andrew Huberman and Dr. David Sinclair’s Insightful Podcast

But before that, let me shed light on my motive behind reviewing this particular conversation. Firstly, the topic of slowing and reversing aging has been of great interest to me for some time. Perhaps because of my own stage in life.

Secondly, I aim to decipher and explore the some what complex terminology used in their discussion. Prior to this, terms like “Sirtuins” remained unfamiliar to me.

This review, therefore, serves as an educational journey for both you, the reader, and myself. Without further ado, let’s delve into the heart of the matter.

Some parts of the conversation have been edited slightly to make the review easier to read.

Andrew Huberman, Ph.D., is a neuroscientist and tenured professor at Stanford School of Medicine.

Dr David Sinclair, a tenured Professor of Genetics at Harvard Medical School.

What are the behavioural tools that one can start to think about in terms of ways to modulate the way that DNA is being expressed, and functioning. What are the sorts of things that people can do to improve the Sirtuin pathway. What what can people do what do you do?

The Sirtuin pathway refers to a group of proteins that play a significant role in regulating several biological processes, including ageing, transcription, apoptosis (cell death), inflammation, and stress resistance.

We know that aerobic exercise in mice and rats raises their NAD levels, and their levels of Sirtuin genes goes up, two actually, number one and number three.

What we don’t know yet is what type of exercise is optimal to get them to change. We will learn, it has been revealed that we’re doing work with the military, in the US, to try and understand that kind of thing.

I’ll always tell you and the public when I don’t know something. I’m not gonna extrapolate. But what do I do, I base my exercise on the scientific literature, which has shown that maintaining muscle mass is very important for a number of reasons.

The two main ones are you want to maintain your hormone levels. I’m an older male losing my testosterone and muscle mass over time. By exercising I will maintain that, and have in fact probably have not had a body like this since I was 20. So that’s one of the benefits of having this lifestyle.

There is data in humans that show that there are some males in their 80s and 90s, where their testosterone levels are equivalent to the average of a 25 and 30 year old. Really impressive studies. This idea that testosterone goes down with age, it might be the trend, but it’s not necessarily a prerequisite.

I think most of us know Testosterone levels decline in men and women as they get older. An estimated average of 1% a year after age 30 in men. In women, levels will decline after menopause, or some where between 45 and 55.

So as you grow older, the level of testosterone gradually decreases. This causes a variety of changes, such as lower energy levels, reduced sex drive. It’s a natural part of ageing, we need to slow down. I need to find these studies.

Right I believe in naturally increasing and maintaining these hormone levels. I’ve been measuring them for a long time and I could see for my testosterone levels were steadily going down. I actually became complacent, and it was the worst actually, my age changed in the wrong direction after that. I was relaxed and not worried about the future.

But then I got serious and actually according to the inside tracker algorithm got my age down from 58 to 31 in a matter of months. That that was a big drop and I’ve been getting steadily younger over the last 10 years according to that measurement the blood test.

What about estrogen because women are different in the sense that they do the number of eggs that they and the ovaries change over time right do you think that they can maintain estrogen levels at in over longer periods of time using some of these same protocols.

If you take a mouse and put it on fasting or caloric restriction, up until the point where it should be infertile, so that’s about a year of age when a mouse gets infertile, due to aging.

The fasting it’s not an extreme fast, it’s just less calories. Then you put them back on a regular food and they become fertile again for many months afterwards. So the effect on slowing down aging is also on the reproductive system.

What I think is really interesting is that what we’re learning from work, that you and your colleagues have done, and in my lab as well, is that the body has remarkable powers of healing and recovering from illness and injury.

What we once thought was a one-way street, and you just can’t repair, you can’t get over these diseases, you can reset the system. The body can really get rejuvenated in ways that in the future will wonder why why didn’t we work on this earlier.

The future of humanity is more like us walking around like Deadpool. We will probably be cleaner and we won’t smell as bad. Deadpool if you don’t know can get injured and just recover. It’s very hard to injure this guy, and we’re going to be the same.

There are many species you cut off the limb, the limb grows back. Salamanders for example, we are now learning how to tap into that system. In part what we are doing is reversing the age of those cells, and telling them how to read the genes correctly again.

Reversing the age of that epigenome, and when you do that the cells, the brain for instance, the skin, we did the optic nerve.

The epigenome is a multitude of chemical compounds and modifications that can be found within the cell, which act as a regulatory system that controls gene expression.

Research has suggested that alterations in the epigenome can be associated with the development of certain diseases, including cancer, neurological disorders, and autoimmune conditions.

Understanding the epigenome has become increasingly important in the fields of genetics, molecular biology, and medicine. It has the potential to provide insights into how environmental factors can influence gene expression, and impact human health and disease.

I want to return to the topic that I took us away from, so I apologize which is behavioural protocols do you regularly do the cold shower thing ice baths cold water swims are you into that whole biz.

I don’t do them regularly, I do try to sleep cool, I sleep better anyway. I try to dress without a lot of warm clothes I’m here in a T-shirt and it’s middle of summer, but in Winter I’ll try to wear a t-shirt too.

So you’re challenging your system to thermoregulate?

Thermoregulation is the process by which the body maintains its internal temperature within a certain range, despite changes in the external environment. The human body strives to maintain a core temperature of around 98.6°F (37°C).

Right, I’ve got this hypothesis with Ray Cronus we published, What’s called the metabolic winter hypothesis. Which in a few tens of thousands of years ago, we were either hungry or cold, or both.

We rarely experienced that now, and so we try to give ourselves the metabolic winter. Part of the problem I think with the Obesity epidemic, is that we’re never cold, when you’re cold you have to burn more energy. It may be only slightly more, but over the whole night if you’re a little bit cool, you’ll actually expend more energy, so I try to do that.

But I’m not a big fan of cold showers. The sauna, I don’t have access to my gym as much as I did, but I do want to get back into it.

I used to do it regularly, I try to compensate with changes in my diet and exercise, until I get back into it.

You reminded me of something that I meant to ask earlier that obesity reduces NAD levels and accelerates aging.

How? is there something direct about white adipose tissue? The reason I ask this there is really interesting data now that fat actually gets neural innervation.

It’s not just stored fuel, it’s stored fuel that’s acting as an endocrine organ essentially. So why would being fat make people age faster?

NAD, or nicotinamide adenine dinucleotide, is a vital coenzyme found in all living cells.

Maintaining proper NAD levels is crucial for cellular energy production, and maintaining cellular health. Changes in NAD levels can impact various cellular functions, and have been linked to aging, metabolism, and certain diseases.

Adipose Tissue

Adipose tissue, commonly known as body fat, is a specialized connective tissue primarily involved in energy storage, thermal insulation, and cushioning of organs.

It serves as a crucial endocrine organ involved in regulating metabolism, insulin sensitivity, and hormone secretion.

Excessive accumulation of adipose tissue can lead to obesity, which is associated with various health risks such as cardiovascular disease, diabetes, and certain types of cancer.

Conversely, too little adipose tissue can result in metabolic disorders and complications related to energy regulation.

Neural Innervation

Neural innervation refers to the distribution of nerves to various tissues and organs in the body. The nervous system plays a crucial role in regulating the functions of adipose tissue through neural innervation

Endocrine Organ

An endocrine organ is a specialized organ or group of cells that produces and secretes hormones directly into the bloodstream.

Examples of endocrine organs include the pituitary gland, thyroid gland, adrenal glands, pancreas, and the gonads (ovaries and testes). These organs play a crucial role in maintaining homeostasis and ensuring the proper functioning of the body’s various systems.

I don’t know but I’ll give you my best answer which is that obesity comes along with a lot of problems that include a lot of senescence cells.

In fact if you stain old fat for senescence cells it lights up, and when you kill off those cells at least in mice and maybe in humans it looks like the fat is less toxic to the body.

Because those senescence cells in their fat are secreting these inflammatory molecules that will accelerate aging as we now know.

You talk about the sort of twins in NAD so if we if we just look philosophically at why this would be. The sertuins only like to come on or get activated when the body needs is under adversity. If a cell is surrounded by fat, or contains a lot of fat, it’s going to think times are good, and doesn’t need to switch on.

So that’s the evolutionary argument. Mechanistically, we don’t know. But it could have something to do with the response to glucose, which then responds to the sertuine gene. But that hasn’t been worked out very well.

Senescent cells are cells that have entered a state of irreversible growth arrest as a response to various stressors, including DNA damage.

Senescence can be beneficial, as it prevents damaged cells from becoming cancerous. However, the accumulation of senescent cells in tissues over time is associated with aging and age-related diseases.

Research into senescent cells has intensified in the field of ageing biology, as scientists are exploring ways to target and eliminate these cells to potentially mitigate age-related diseases and extend healthy lifespan.

So why is it that, having elevated blood sugar, glucose and Insulin ages us more quickly and or why is it that having periods of time each day, or perhaps longer, (of not eating), can extend our lifespan?

Let’s start with with what I think was a big mistake was the idea that people should never be hungry. We live in a world now where there’s at least three meals a day, and then we’ve got companies selling bars and snacks in between.

So the feeling of hunger, some people never experience hunger their whole lives, it’s really really bad for them.

It was based I believe on the 20th century view that you don’t want to stress out the pancreas, and you try to keep insulin levels pretty steady and not have this this fluctuation.

What we actually found my colleagues and I, across this field of longevity is that when you look at first of all animals, whether it’s a dog or a mouse or a monkey, the ones that live the longest by far, 30% longer and stay healthy, are the ones that don’t eat all the time.

It was actually first discovered back in the early 20th century but people ignored it.

Then it was rediscovered in the 1930s Clive McKay. He did caloric restriction, he put cellulose in the food of rats. That way they couldn’t get as many calories, even though they ate, those rats lived 30% longer.

But then it it went away, and then it came back in the 2000s in a big way.

Then a couple of things happened. One is that longevity genes in the body that come on and protect us from aging and disease. The group of genes that I work on are called sirtuins, there’s seven of them.

We showed in 2005 in a science paper, that if you have low levels of insulin, and another molecule called insulin-like growth factor, those low levels turn on the longevity genes.

One of them that’s really important is called sert1. But by having high levels of insulin all day, being fed means your longevity genes are not switched on, so you’re falling apart.

Your epigenome your information that keeps your cells functioning, over time just degrades quicker. Your clock is ticking faster by always being fed.

The other thing I think might be happening, by always having food around, is that it’s not allowing the cell to have periods of rest and re-establish the epigenome.

SIRT1: This sirtuin is involved in regulating cellular responses to stress and is associated with longevity.

SIRT2: This sirtuin is primarily found in the cytoplasm and is involved in the regulation of the cell cycle.

SIRT3: This sirtuin is localized in the mitochondria and is associated with regulating mitochondrial function and metabolism.

SIRT4: This sirtuin is also located in the mitochondria and is involved in regulating metabolism.

SIRT5: This sirtuin is primarily found in the mitochondria and is involved in regulating metabolic enzymes.

SIRT6: This sirtuin is primarily located in the nucleus and is associated with regulating genome stability and DNA repair.

SIRT7: This sirtuin is also primarily located in the nucleus and is involved in regulating RNA polymerase I transcription.

These sirtuins play essential roles in various cellular processes and have been the subject of extensive research in the fields of ageing, metabolism, and longevity.

I feel I need to address Dr. Sinclairs first comment at the beginning of this last section, when he stated the following…

“Let’s start with with what I think was a big mistake was the idea that people should never be hungry. We live in a world now where there’s at least three meals a day, and then we’ve got companies selling bars and snacks in between”.

While obesity is a problem in many countries, there is still a percentage of starving people in the world today.

According to Action Against Hunger, there is more than enough food produced in the world to feed everyone on the planet. Yet as many as 783 million people still go hungry. This includes 14 million Children Suffer from Severe Acute Malnutrition.

Here is a link to their website if you want to find out more.

https://www.actionagainsthunger.org/the-hunger-crisis/world-hunger-facts/

• Aerobic exercise in mice and rats, and they believe people, can raise NAD levels and Sirtuin gene expression, but the optimal type of exercise for this effect is still being researched.
• Maintaining muscle mass is crucial for maintaining hormone levels, especially for older individuals to preserve testosterone and muscle mass.
• Some males in their 80s and 90s have testosterone levels equivalent to those of 25 and 30-year-olds, which suggests that age-related decline in testosterone might not be inevitable.
• Fasting or caloric restriction in mice has shown it can lead to fertility restoration even after the point of expected infertility due to aging. Indicating the potential effects on slowing down the body ageing process.
• The body has the ability to heal and recover from illness and injury, which suggests the potential for rejuvenation and reversal of the aging process in the future.
• Periods of not eating and intermittent fasting can extend lifespan by activating the body’s defensive genes and turning on longevity genes like Sirtuins.
• Skipping a meal a day, preferably at the beginning or end of the day, can be an effective approach to intermittent fasting.
• Regulating blood sugar levels through dietary practices can prevent energy crashes and provide sustained focus throughout the day.
• Avoiding simple carbohydrates, and excessive sugar consumption, can help maintain a healthy diet and stable blood sugar levels.
• Finally, Don’t get run over by a bus.

Q: What are Sirtuins and why are they important?

A: Sirtuins are a group of seven proteins that regulate biological processes including aging, cell death, inflammation, and stress resistance. They’re crucial for longevity and are activated during periods of stress or caloric restriction.

Q: How does obesity affect aging?

A: Obesity accelerates aging through multiple mechanisms, including:

– Increased senescent cell accumulation

– Reduced NAD levels

– Decreased activation of longevity genes

– Chronic inflammation

Q: Can testosterone levels be maintained with age?

A: Yes, studies show some men in their 80s and 90s maintain testosterone levels equivalent to 25-30 year olds through proper exercise and lifestyle choices.

Q: What role does fasting play in longevity?

A: Fasting activates longevity genes, allows cellular repair, and can extend lifespan by:

– Activating Sirtuin genes

– Lowering insulin levels

– Allowing cellular rest and repair

– Promoting metabolic flexibility

Q: How does exercise influence aging?

A: Exercise helps slow aging by:

– Increasing NAD levels

– Activating Sirtuin genes

– Maintaining muscle mass

– Regulating hormone levels

– Supporting overall metabolic health

So I hope you learnt something? I know I did. Feel free to leave a comment.

Below is the section of the podcast this article is based on.

Review by Bob Kerr. That’s Life 247 Admin.