Today, we’re going to be talking about Deregulated Nutrient Sensing, one of the Hallmarks of Aging.
This is turning out to be one of the most important hallmarks in the fight to reverse the aging process,
Most of the medications used by the longevity community to fight aging
have been developed to combat this one halmark.
So stick around to learn more.
As we all know, nutrients are essential for all living things, both plants and animals.
And the amount of nutrients that are present in the microcellular environment
inform the cells about whether or not it’s a good time to grow.
The cell’s ability to detect this is a crucial aspect of our health.
Unfortunately, this ability to detect the nutrients that are available to the cells,
the ability to sense the nutrients, changes as we age.
And it doesn’t change in a way that’s beneficial to us.
This particular Hallmark of Aging, deregulated nutrient sensing,
marks a shift in how our cells detect and measure the abundance, or lack thereof,
of the nutrients that are available to them.
Nutrient sensing is a mechanism that cells use to recognize and react to useful fuel substrates
such as protein, glucose, fats…even substances like vitamin B.
And each type of fuel used by the cells requires a separate pathway, and separate molecules.
Multiple nutrient-sensing pathways are required
to ensure that our bodies take in the right amount of nutrients.
By taking in the correct amounts of nutrients, our bodies can produce the molecules that they need at the time,
while conserving resources.
Now, when we’re young, the body is very adept at recognizing nutrients and directing the flow of traffic.
But as we age, the bodies ability to perform this function declines.
And as our bodies lose the ability to detect and react to nutrients,
this loss of ability can in turn have a dramatic effect on aging.
Sort of a biofeedback loop.
A study published in the Nature Journal of Science, by Alejo Efeyan,
found that nutrient-sensing pathways are commonly de-regulated in human metabolic diseases.
Oxidative stress and mitochondrial dysfunction can gradually damage cells over time,
and as this damage accumulates, a side effect of this is the deregulation of nutrient-sensing molecules.
And this can lead to a host of adverse consequences that include high blood pressure, abnormal cholesterol,
excess body fat and the development of metabolic syndrome, obesity and diabetes.
It can also intensify chronic inflammation.
And, of course, due to that biofeedback loop,
this can in turn lead to ever-increasing deregulated nutrient sensing.
And now we’re locked in a downward spiral.
Nutrient sensing consists of four separate pathways.
Two of them, the mTOR and the IIS pathway,
detect high nutrient levels, and the other two, the AMPK and the SIRT pathways,
are used to detect low nutrient levels.
And these two sets of pathways have opposite effects on aging.
While activation of the mTOR or the IIS pathways tend to accelerate aging and shorten lifespans,
activation of the AMPK or the SIRT pathways do just the opposite.
They slow aging down and extend both lifespans and health spans,
which is the amount of time an human stays healthy and active.
So, let’s take a quick look at each of these pathways, starting with the IIS pathway.
IIS stands for “Insulin and Insulin-Like Growth Factor.”
Insulin-like growth factor is produced in the liver and it’s production is stimulated by Human Growth Hormone.
It is also a hormone,
and it’s molecular structure is similar to that of insulin and both hormones can sense the presence of glucose.
Both are used anabolically, to create new tissue.
And both are part of the IIS pathway.
mTOR, on the other hand, senses amino acids, particularly the amino acid methionine.
The mTOR pathway is comprised to 2 complexes:
mTORC 1, or mTOR Complex 1, and mTORC 2, and these complexes are, in a word, complex.
Like the IIS pathway, mTOR is used anabolically to create new tissue.
Both of these pathways increase metabolism,
and when cells are more active,
they produce more waste products and they create and accumulate more damage.
Reducing growth and slowing the metabolism is thought to protect cells in much the same way that
running an engine at a lower speed can protect it from damage caused by overheating.
And here’s the thing.
They’re are both important pathways, and when they’re activated, they both serve important functions.
Activation of both pathways is required for the building or repair of muscle tissue, for the healing of wounds,
and for the maintenance of energy levels.
Since lower activity of both of these pathways can lead to longer lifespans,
suppression of these pathways is often touted as being beneficial to longevity.
However, I believe that “balance” is the key here.
You don’t want to “over-activate” them,
but you certainly want to activate them enough to maintain bodily functions.
OK, let’s move on to the catabolic pathways.
AMPK stand for AMP-activated kinase.
A kinase is simply an enzyme that is used to transport phosphate groups, which is how energy is created.
ATP, or adenosine triphosphate, is the universal energy source for all cellular activity.
ATP creates energy by giving up a phosphate group, creating AMP, or adenosine monophosphate,
or ADP…adenosine diphosphate.
AMPK senses both AMP and ADP, which are present in higher quantities when nutrients are scarce.
So AMPK is a sensor of fasted or calorie-restricted states,
and it regulates the metabolism by adding phosphates to serine and threonine, which are both amino acids.
And finally, we have the SIRT pathway.
SIRT1-7 are the names for both the genes and the enzymes that they encode for,
and they’re also known as sirtuins.
Sirtuins are a family of proteins that are dependent on NAD+, and they’re called “the longevity genes.”
They regulate mitochondrial biogenesis, they stimulate apoptosis and autophagy, they inhibit inflammation,
they stimulate chemical signaling, they repair DNA and they help control gene expression.
They also help control catabolic metabolism.
The SIRT pathway can detect when energy levels are low by sensing the coinciding increase in NAD+.
Upregulating some of the sirtuins have been demonstrated to promote longevity.
So, what can you do to help keep these various pathways in balance and extend your lifespan?
Well, there are several things you can do.
The first is to improve your diet.
Eating junk food or highly processed and refined foods can wreak havoc on your nutrient sensing pathways.
So, eating healthy foods is a great way to improve nutrient sensing.
And by healthy foods, I mean whole, organic, un-processed and un-refined foods.
Foods like fruits and vegetables and healthy fats.
Now, avoiding proteins, like meats, will suppress the mTOR pathway,
but you need protein for building muscle tissue and staving off sarcopenia,
the chronic loss of muscle mass associated the aging.
This is an issue that I find conflicting information on, and I haven’t come to a really good decision on this yet.
I may be doing a video on the right amount of protein to eat in the future,
taking into consideration things like building muscle vs. suppressing the mTOR pathway, for example.
If this is something you’d like to see, leave me a comment.
You can also suppress the mTOR pathway by judicious use of the drug rapamycin.
But this isn’t something that I personally am ready to try yet, for a number of reasons.
Perhaps a better way to suppress the mTOR pahtway, or better yet, keep it in balance,
is to activate the AMPK pathway.
These pathways are interconnected, with SIRT having an impact on IIS,
and with AMPK shutting down one of the mTOR complexes.
And you can activate AMPK by doing exercise.
Studies have shown that AMPK can be activated by contraction of muscle tissue,
and one of the best exercise for activating the AMPK pathway is doing high intensity interval training.
Intermittent fasting also activates AMPK.
Taking a supplement to increase NAD+ levels, like nicotinamide riboside or nicotinamide mono nucleotide,
better known as NR and NMN, respectively, can improve SIRT levels.
Taking the drug metformin is another way to up regulate SIRT.
Hope you enjoyed this video.
If you want to learn more about some of the individual nutrient sensing pathways,
you might want to check out this playlist.
That’s it for me, I’m outta here.
Catch you next time.