Andrew Huberman "Aging is a Treatable disease"

Summary

In this discussion, the role of behavioral tools in modulating DNA expression and function is explored. The speaker emphasizes the significance of aerobic exercise in raising NAD levels and maintaining muscle mass, which helps preserve hormone levels, particularly testosterone. They also touch on the potential of caloric restriction in mice to delay aging and fertility, hinting at similar effects in humans. The conversation delves into the metabolic winter hypothesis, suggesting that mimicking past conditions of hunger and cold may have metabolic benefits. The speaker advocates for intermittent fasting, skipping meals to allow the body to activate longevity genes and maintain a steady blood sugar level, which they personally practice by skipping breakfast.

Takeaways

• 🏃 Aerobic exercise, as demonstrated in mice and rats, can increase NAD levels and upregulate certain genes, although the optimal type of exercise is still being researched.
• 💪 Maintaining muscle mass through exercise is crucial for hormone level regulation, particularly for older males to preserve testosterone levels.
• 🔬 Scientific literature supports the idea that naturally increasing and maintaining hormone levels can have significant health benefits, as evidenced by some males in their 80s and 90s having testosterone levels comparable to younger adults.
• 🧊 Cold exposure, such as cold showers or ice baths, is not regularly practiced by the speaker, but they do advocate for sleeping cool and dressing lightly to challenge the body's thermoregulation.
• 🌡 The 'metabolic winter hypothesis' suggests that occasional cold exposure can mimic historical survival conditions, potentially aiding in metabolism and energy expenditure.
• 🚫 Obesity is linked to reduced NAD levels and accelerated aging, possibly due to the inflammatory molecules secreted by senescent cells in fat tissue.
• 🍽 Intermittent fasting and caloric restriction have been shown to extend lifespan and improve healthspan in various species, including potential benefits for humans.
• ⏳ The speaker recommends skipping a meal a day as an easy starting point for intermittent fasting, suggesting it helps regulate blood sugar levels and prevent energy crashes.
• 🥗 A diet low in sugar and simple carbohydrates, with a focus on vegetables and occasional protein, is suggested for better health and possibly reduced plaque buildup.
• 🧠 The body's remarkable ability to heal and recover from illness and injury is highlighted, with ongoing research aiming to tap into these natural regenerative processes.

Q & A

What is the relationship between aerobic exercise and NAD levels in mice and rats?

Aerobic exercise in mice and rats has been shown to raise their NAD levels, which is important for maintaining certain genes' expression.

What is the significance of maintaining muscle mass through exercise?

Maintaining muscle mass is crucial for preserving hormone levels, such as testosterone in older males, which can help maintain a youthful physique and health.

How can fasting or caloric restriction impact fertility in mice?

Fasting or caloric restriction can temporarily make mice infertile, but once they are returned to regular food, their fertility can be restored for an extended period.

What is the 'metabolic winter hypothesis' mentioned in the script?

The 'metabolic winter hypothesis' suggests that our ancestors experienced periods of hunger and cold, which our modern lifestyle lacks. Emulating this by sleeping cool or avoiding excessive warmth may help maintain metabolic health.

How does obesity affect NAD levels and aging according to the script?

Obesity is associated with reduced NAD levels and accelerated aging. It introduces problems like increased senescent cells in fat tissue, which secrete inflammatory molecules contributing to aging.

What is the role of sirtuins in the context of aging and diet mentioned in the script?

Sirtuins are a group of longevity genes that are activated under conditions of low insulin and insulin-like growth factor, which can be achieved through dietary restrictions.

Why is it important to have periods of not being fed according to the script?

Having periods of not being fed allows the body to activate defensive genes, improve insulin sensitivity, and potentially extend lifespan by maintaining cellular health.

What is the significance of the study by Rafael De Cabo mentioned in the script?

Rafael De Cabo's study with mice showed that the timing of food intake, rather than the specific diet composition, was crucial for longevity, with mice eating within a limited time window living longer.

What is the recommended approach to intermittent fasting according to the script?

The script suggests skipping a meal a day, preferably breakfast or dinner, to align with the sleep period and promote health benefits associated with fasting.

How does the speaker in the script manage their diet to avoid sugar and simple carbohydrates?

The speaker avoids sugar and simple carbohydrates by not eating dessert and minimizing bread intake, which has also led to a reduction in dental plaque.

What are the potential benefits of cold exposure mentioned in the script?

Cold exposure can challenge the body to thermoregulate, potentially increasing energy expenditure and aligning with the 'metabolic winter hypothesis' for improved metabolic health.

Outlines

00:00

💪 Behavioral Tools for DNA Expression and Exercise

The first paragraph discusses behavioral tools that can influence DNA expression and function. It highlights the impact of aerobic exercise on NAD levels in mice and rats, and the subsequent increase in certain gene expressions. The speaker acknowledges the need for further research to determine the optimal type of exercise for these changes. The conversation also touches on the importance of maintaining muscle mass to preserve hormone levels, particularly testosterone in older males. The speaker shares personal experiences with exercise and its benefits on hormone levels and general health, including a significant reduction in biological age as measured by an internal algorithm. The paragraph concludes with a discussion on the potential for the human body to heal and rejuvenate, drawing parallels to regenerative abilities seen in other species like salamanders.

05:00

🌡️ Metabolic Winter Hypothesis and Obesity's Impact on Aging

The second paragraph delves into the 'metabolic winter hypothesis,' which suggests that historical experiences of hunger and cold have metabolic benefits that are lacking in modern lifestyles. The speaker hypothesizes that a lack of cold exposure and constant warmth might contribute to obesity and its associated health issues, including reduced NAD levels and accelerated aging. The discussion moves to the role of white adipose tissue as an endocrine organ and its potential impact on aging. The speaker also explores the evolutionary and mechanistic reasons why obesity might lead to faster aging, including the presence of senescent cells in fat and their secretion of inflammatory molecules. The paragraph concludes with a critique of the modern practice of constant feeding and its detrimental effects on longevity genes and the epigenome.

10:01

🥗 Intermittent Fasting and Its Effects on Longevity

The third paragraph focuses on the benefits of intermittent fasting for longevity. It discusses the importance of experiencing hunger and the negative impacts of constant food availability on health and aging. The speaker references historical and recent studies that show animals live longer when they do not eat all the time. The conversation highlights the role of sirtuins, a group of longevity genes, which are activated by low insulin levels. The speaker also mentions the importance of allowing the body periods of rest to re-establish the epigenome. The paragraph includes a discussion on the benefits of lower glucose levels and the impact of meal timing on longevity, with the speaker suggesting that the 'when' of eating is more critical than the 'what.' The speaker shares personal fasting practices, advocating for skipping meals and focusing on liquid intake during the day to maintain steady blood sugar levels and avoid energy crashes.

Keywords

💡DNA Expression

DNA expression refers to the process by which information from a gene is used in the synthesis of a functional gene product. In the video, the discussion revolves around how certain behaviors can modulate DNA expression, meaning how lifestyle choices can influence the way genes are activated or deactivated. The script mentions that aerobic exercise in mice and rats can raise NAD levels, which is linked to changes in gene expression, suggesting that physical activity is one way to influence this process.

💡NAD Levels

NAD, or nicotinamide adenine dinucleotide, is a coenzyme found in all living cells and is a key factor in cellular respiration. The video script discusses how aerobic exercise can raise NAD levels in mice and rats, which is significant because NAD is associated with the regulation of DNA repair and other biological functions. The script implies that maintaining or increasing NAD levels could be a strategy for improving health and possibly extending lifespan.

💡Exercise

Exercise is any bodily activity that enhances or maintains physical fitness and overall health. The video script emphasizes the importance of exercise, particularly aerobic exercise, in modulating gene expression and hormone levels. The speaker shares personal experiences, noting that maintaining muscle mass through exercise is crucial for hormone regulation, and they have observed improvements in their own body composition and health markers as a result of their exercise routine.

💡Hormone Levels

Hormone levels refer to the concentration of hormones in the body, which are chemical messengers that regulate various physiological processes. The video discusses the importance of maintaining hormone levels, especially testosterone in older males, through exercise and lifestyle choices. The script mentions that some males in their 80s and 90s can maintain testosterone levels equivalent to those of much younger men, suggesting that age-related hormone decline is not inevitable.

💡Caloric Restriction

Caloric restriction involves reducing the intake of calories without malnutrition. The script mentions that caloric restriction, such as fasting, can extend the lifespan of mice and improve their health. It suggests that this method can slow down the aging process and potentially rejuvenate the body by influencing the reproductive system and other physiological functions.

💡Sirtuins

Sirtuins are a family of proteins that play a role in regulating cellular processes associated with aging, including DNA repair and cell survival. The video script discusses sirtuins in the context of longevity genes that are activated under conditions of stress or adversity, such as fasting. The speaker's research indicates that low insulin levels can activate sirtuins, which may contribute to longevity.

💡Intermittent Fasting

Intermittent fasting is an eating pattern that cycles between periods of eating and fasting. The video script suggests that intermittent fasting can be a beneficial practice for health and longevity. The speaker recommends skipping a meal a day as a simple way to start intermittent fasting, which can help regulate blood sugar levels and potentially activate longevity genes.

💡Epigenome

The epigenome consists of chemical compounds that can switch genes on or off. It is a crucial factor in how genes are expressed and how cells function over time. The video script discusses the idea of reversing the age of the epigenome, which means resetting the cellular aging process. This is significant because it suggests that it might be possible to rejuvenate cells and tissues, potentially leading to improved health and longevity.

💡Inflammation

Inflammation is part of the immune response to harmful stimuli, including damaged cells, irritants, or pathogens. The video script mentions that senescent cells in fat tissue can secrete inflammatory molecules that accelerate aging. This highlights the role of inflammation in the aging process and the potential benefits of reducing it through lifestyle interventions.

💡Glucose and Insulin

Glucose is a simple sugar that is the primary source of energy for cells, and insulin is a hormone that regulates glucose uptake by cells. The video script discusses the relationship between glucose and insulin levels and aging. High levels of insulin from constant feeding can suppress the activation of longevity genes, while periods of fasting can lower insulin levels and potentially extend lifespan by activating these genes.

Highlights

Aerobic exercise in mice and rats raises NAD levels and affects gene expression.

Exercise type to optimize NAD levels is currently under investigation with the US military.

Maintaining muscle mass is crucial for hormone level regulation, especially in older males.

Exercise can help maintain testosterone levels, even in older individuals.

There are humans in their 80s and 90s with testosterone levels equivalent to those in their 20s and 30s.

Fasting or caloric restriction can temporarily make mice infertile, but fertility can be restored.

The body has remarkable powers of healing and recovery, which can reset and rejuvenate systems.

Reversing the age of cells and the epigenome can lead to rejuvenation.

Cold exposure and thermoregulation are part of the 'metabolic winter hypothesis'.

Obesity is linked to reduced NAD levels and accelerated aging.

Fat tissue acts as an endocrine organ and can influence aging through senescent cells.

Elevated blood sugar and insulin levels can age the body more quickly.

Intermittent fasting can extend lifespan by activating longevity genes.

The timing of food intake, rather than the content, is crucial for longevity.

Skipping meals, especially breakfast or dinner, can be an effective approach to intermittent fasting.

Adapting to intermittent fasting can lead to steadier blood sugar levels and improved focus.

A diet low in sugar and simple carbohydrates can improve dental health by reducing plaque.

Transcripts

what are the behavioral tools that one

can start to think about in terms of

ways to modulate these uh you know

basically the way that DNA is is being

expressed and functioning in other words

what are the sorts of things that people

can do to improve this or two and

pathway and I I realize that there are

caveats we can't go directly from a

behavior disc or twins but in the

general theme what what can people do

what do you do right well we know that

that aerobic exercise in mice and rats

raises their NAD levels and and their

levels of certain one of the genes goes

up uh two actually number one and number

three what we don't know yet is what

type of exercise is optimal to get them

change we will learn we're doing work

now it's revealed that we're doing work

with the military in the US to try and

understand that kind of thing

and 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 and by exercising

I will maintain that and have uh in fact

I've I probably haven't had a body like

this since I was 20 so that's one of the

benefits of having this lifestyle there

are data in humans that show that there

are some

males in their 80s and 90s where their

testosterone is equivalent to the

average of 25 and 30 year olds really

impressive studies this idea that

testosterone goes down with age

um it might it might be the trend but

it's not necessarily a prerequisite

right I believe in in naturally

increasing and maintaining these hormone

levels and I've been measuring them for

a long time and I could see for me my

testosterone levels were steadily levels

were going down and then you got tenure

and they went back up again uh I

actually became complacent and and uh it

was the worst actually my age changed in

the wrong direction after that because I

was relaxed interesting and not worried

about the future

um but then I got serious and actually

according to the inside dracral

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 uh

the number of eggs that they and the

ovaries change over time right do you

think that they can maintain estrogen

levels at in uh over longer periods of

time using some of these same protocols

if you take a mouse and put it on

fasting or caloric restriction

form

up until the point where it should be

infertile so that's about it at a year

of age a mouse gets in Fertile female

Mouse due to due to fasting simply to

aging due to aging due to aging the

fasting it's 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 many

months afterwards so the the effect on

slowing down aging is also on the

reproductive system interesting 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 and 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

and 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 will

probably be cleaner and we won't smell

as badly but

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 or yeah we are

now learning how to tap into that system

and in part what we're 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 are the

skin uh we did the optic nerve

um I want to return to the topic that I

took us away from so I apologize which

is behavioral 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

um I I do try to sleep cool

um I sleep better anyway I try to dress

without a lot of warm clothes I'm

hearing 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 right right I've got this

uh hypothesis with Ray Cronus 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 and

we really experienced that now and so we

try to give ourselves the metabolic

winter and part of the problem I think

with the Obesity epidemic is that we're

never cold and cold when you're cold you

have to burn energy it may be only

slightly 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

um the sauna I don't have access to my

gym as much as I did so 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 and the reason I

ask this there are 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 um yeah

why would being fat make people age

faster don't know but I'll give you my

best answer which is that

obesity comes along with a lot of

problems that uh include a lot of

senescent cells in fact if you stain old

fat for senescent cells it lights up and

when you kill off those cells at least

in mice and maybe in humans it looks

like

um the fat is less toxic to the body

because those senescent 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

um

so if we if we just look philosophically

at why this would be the sirtuins only

like to come on or get activated when

the body needs is under adversity and if

a cell is surrounded by fat or contains

a lot of fat it's going to think times

are good 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 certain Gene but that hasn't been

worked out very well 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 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 hog riding their whole lives

it's really really bad for them

um 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

um and not have this this fluctuation

what we actually found uh 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

I'm actually was first discovered back

in the early 20th century but people

ignored it

and then it was rediscovered in the

1930s Clive McKay did Clark restriction

he put

cellulose in the food of rats so they

couldn't get as many calories even

though they ate and those rats lived 30

longer but then it it went away and then

it came back in the 2000s in a big way

when 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

and we showed in 2005 uh 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 sort one and 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 and

re-establish the epigenome and so it

also is accelerating in that direction

there's plenty of other reasons as well

that are not as profound such as

um having low levels of glucose in your

body will trigger your major muscles in

your brain to become more sensitive to

insulin and suck the glucose out of your

bloodstream which is very good you don't

want to have glucose flowing around too

much and that will ward off type 2

diabetes do you think there's anything

about the subjective experience of

hunger itself that could be beneficial

for longevity there are some studies

that are being done at the National

Institutes of Health that are able to

simulate the effect of hunger but still

provide the calories and it's looking

like there's a small component that's

due to hunger but most of it actually is

because you've got this these periods of

not being fed and then the body turns on

these defensive genes

um there's a really interesting

experiment that was published maybe a

couple of years ago by Rafael De Cabo

down at the NIH what he did was he took

over ten thousand mice and gave them

different combinations of fat

carbohydrate protein and he was trying

to figure out what was the best

combination and then he also cleverly

had a group

well two groups one that was fed all the

time or eight as much as they wanted and

the other group was only given food for

an hour a day and it turns out they ate

roughly the same amount of calories

because of course in an hour they're

stuffing their faces uh it turns out it

didn't matter what diet he gave them it

was only the group that ate within that

window that lived longer and

dramatically longer

so my conclusion is

and mice are very similar to us

metabolically I think that tells us that

it's not as important what you eat it's

when you eat during the day what is the

protocol that people can extrapolate

from that

um or maybe I should just ask you what

is your protocol

for when to eat and when to avoid food

do you fast do you ever fast longer than

24 hours what do you do and what do you

think is a good jumping off place if

people want to explore this as a

protocol well if there's one thing I I

could say if I would say definitely try

to skip a meal a day that's the best

thing does it matter which meal or the

essentially equivalent well as long as

it's at the end or the beginning of the

day because then you you add that to the

sleep period where you're hopefully not

eating I think that's an excellent point

I realize it's a simple one but I think

it's an excellent one because I think

one of the things that people struggle

with the most is knowing how when and

how to initiate this so-called

intermittent fasting in the middle of

the day obviously is not tacked to The

Sleep Cycle in the same way so it's much

harder as well for many people yeah yeah

well I'll tell you what I do

um I I skip breakfast I have a tiny bit

of yogurt or olive oil because the

supplements I have need to be dissolved

in it and then I go throughout the whole

day as I'm doing right now here with

this uh this glass of water here I'm

just keeping myself filled with liquids

and so I don't feel hungry beware that

the first two to three weeks when you

try that you will feel hungry and you

also have a habit of wanting to chew on

something that there's a lot of physical

parts to it but try to make it through

the first three weeks and do without

breakfast or do without dinner

uh and you'll get through it and I did

that most for most of my life actually

uh mainly because I didn't I wasn't

hungry in the morning some people are

very hungry in the morning and they may

want to consider skipping dinner instead

but I will go throughout the whole day I

don't get the crashes of the high

glucose and the low glucose that anyone

who goes oh man it's three o'clock I'm

gonna need a sleep if you do what I do

you will not experience that anymore

because what my body does is it's it

regulates blood sugar levels naturally

my liver is putting out glucose when it

needs to and it's very steady and gives

me pure Focus throughout the day and I

don't even have to think about lunch I'm

just powering through

at dinner I mean I love food as much as

anybody so I will I will eat a regular

pretty healthy meal I'll eat I'll try to

eat mostly vegetables I can eat some

fish some shrimp

um I really will eat a steak

um in fact my microbiome is so adapted

to my diet now if I eat a steak it will

not get digested very well I'll feel

terrible rarely eat dessert I gave up

dessert and sugar in my when I turned

40. and um occasionally I'll steal a bit

of dessert because it doesn't hurt if

you steal it right but other than that I

avoid sugar which includes simple

carbohydrates

um bread I try to avoid I've actually

noticed this is a just a side note I

used to get build up of plaque pretty

easily uh and every time I went to the

dentist they'd have to scrape it off and

I even bought tools to scrape it off

because it was driving me nuts I don't

get plaque anymore and I think it's

because of my diet I don't have those

sugars in my mouth that the bacteria

feed on and then form the biofilm on the

teeth