Andrew Huberman "Aging is a Treatable disease"
Summary
TLDRIn 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
💪 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.
🌡️ 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.
🥗 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.
Mindmap
Keywords
💡DNA Expression
💡NAD Levels
💡Exercise
💡Hormone Levels
💡Caloric Restriction
💡Sirtuins
💡Intermittent Fasting
💡Epigenome
💡Inflammation
💡Glucose and Insulin
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
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