We’re all here because we want to stop the aging process, or at least slow it down, right?
But how many of you know what the causes of aging are?
I’m talking about the cellular processes that begin to break down as we grow older,
that are the aging process.
A ground-breaking paper published a few years ago
identified 9 of these cellular processes that cause us to grow old, and that’s what we’re going to talk about today.
The Hallmarks of Aging.
If you’re trying to slow or even reverse the aging process, if you’re trying to turn back the clock on aging…
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that summarizes everything we’re going to cover in this discussion
about the cellular processes that contribute to aging.
In 2013 a landmark paper was published, titled the “Hallmarks of Aging.”
This paper laid out 9 fundamental causes of aging.
Now, while I’m planning on doing a separate video on each of the 9 hallmarks,
today I’m just going to give an overview of all 9 of them.
I feel that this is a really important video because these 9 hallmarks are the aging processes that are going on in each of us.
They're also the avenues of research that are being pursued by biohealth firms to defeat aging.
Understanding what these processes are, how they work, what causes them and how to treat them
are fundamental for anyone hoping to turn back the clock on aging.
This video, and the follow on videos, will lay the groundwork for that understanding.
OK, so this “Hallmarks of Aging” paper was groundbreaking,
and is one of the most widely-quoted and highly regarded papers in the field of longevity research.
It was authored by Carlos Lopez-Otin,
a professor of Biochemistry and Molecular Biology at the Universidad de Oviedo in Spain.
His paper sparked a revolution in longevity research,
laying out the groundwork for a new way of looking at aging…
as a series of accumulated damage at the cellular level that takes place over an extended period of time.
Damage that could be slowed down or even cleared out and reversed,
resulting in rejuvenation and not only an extended lifespan, but an extended health span…
that period of time during which one is healthy, strong and vital.
And it has spurred many scientists into research to conquer the aging process,
and has lead to an explosion of new bio health firms that are exploring ways to defeat aging.
Now, this paper identified 9 fundamental causes of aging, or hallmarks,
and they include Genomic Instability, Telemere Attrition, Epigenetic Alterations, Loss of Proteostasis,
Deregulated Nutrient Sensing, Mitochondrial Dysfunction, Cellular Senescence, Stem Cell Exhaustion
and Altered Intracellular Communication.
The paper divided them into three categories.
The first category are the primary hallmarks, the ones that cause most of the initial damage.
These hallmarks are interrelated, affecting each other in vicious cycles,
and they affect other types of hallmarks that are downstream from them.
The next category is called compensatory or response hallmarks
because these are physiological changes that come about either in response to the primary hallmarks,
or as a way of compensating for them.
Now, in theory, since these hallmarks are in response to the primary category,
stopping the primary could reduce the effects of the compensatory hallmarks.
The third category is called the integrative hallmarks,
and these are downstream from both the primary and the compensatory hallmarks.
These hallmarks lead to a decline in function in a number of bodily and cellular processes.
So, the primary hallmarks lead to the compensatory, which in turn leads to the integrative hallmarks.
Stopping or reducing any of the upstream hallmarks will have an impact on everything downstream from there.
OK, let’s jump into the 9 hallmarks of aging, starting with the primary category…the initial damage that occurs.
The first of these hallmarks is genomic instability, also known as genetic instability,
and this refers to the high incidence of mutation that occurs within the genome.
The human genome contains 3 billion base pairs of DNA,
and the sequence of these pairs undergoes between 10,000 and 100,000 instances of molecular lesions per cell per day.
Now, the body has repair mechanisms to catch these errors,
but as we age, these repair processes become less efficient
and unrepaired molecular lesions to the genetic code fall through the cracks.
Over time, these errors add up.
The human body produces a constant flow of proteins and other materials
that are built according to the blueprints in our DNA, and are the result of gene expression…
the turning on and off of genes.
Errors in the DNA can affect genes and their transcription, and this can result in dysfunctional cells.
This is especially important when those cells are stem cells.
The next hallmark is telomere attrition.
Telomeres are end caps on the chromosomes, kind of like the plastic ends of shoelaces.
They’re composed of DNA and they protect the DNA in the chromosome from damage due to exposure.
Every time a cell divides, a little piece of the telomere is lost, and over time they become shorter and shorter
…until eventually the DNA of the chromosome is exposed, and susceptible to damage.
The telomeres act as a clock to control the number of times a cell can divide, limiting it to about 50 times.
Telomere shortening, or attrition, can lead to genomic instability
and is thought to be a leading cause of cellular senescence.
The third hallmark of aging is epigenetic alterations.
The epigenome is made up of all the chemical compounds that have been added to the genome, or the DNA.
These compounds alter the activity of the genes, or their expression.
These compounds are modifications to the DNA that don’t affect the actual sequence of the DNA.
So these are changes to the genome that are on top of the genetic code.
These changes can turn genes on or off, and can harm the fundamental functions of the cells,
increasing the risk for cancer or other age-related diseases.
And here’s the thing…epigenetic alterations are not permanent, so in theory, these changes can be reversed.
Proteostatsis is when the machinery that produces proteins is working perfectly,
and the last hallmark in the primary category is the loss of proteostasis.
Proteins are large, complex molecules that regulate almost everything in the body,
and they’re made up of hundreds, or even thousands, of smaller parts called amino acids.
How a protein functions is determined by the sequence in which amino acids are connected and how a protein is folded.
Folding can expose certain genes and block or hide others, determining which genes get expressed.
The body tries to keep the production of proteins stable and without any defects.
But sometimes, this process can fail, leading to too many or too few proteins,
or to proteins that are misfolded and bent out of shape.
These misfolded proteins can’t perform their job correctly
and can cause rogue behavior in the cell by giving the wrong instructions.
Worse, these misfolded proteins can bind to one another and form aggregates.
These aggregates can accumulate and cause damage.
Now, normally, these damaged proteins are cleared out by autophagy,
a process that recycles cellular components.
But as we age, the process of autophagy breaks down, and these damaged proteins start to accumulate.
Now we’re going to move on to the second category of hallmarks, called compensatory or response hallmarks.
These are hallmarks that are in response of the primary hallmarks and cause physiological changes.
And the first of these is deregulated nutrient sensing.
We have multiple nutrient-sensing pathways, such as mTOR and AMPK,
that make sure that we’re getting the correct amount of nutrients.
Metabolic changes can lead to these pathways becoming deregulated.
Metabolic activities can also stress out the cells,
whether through too much food intake or the wrong nutrient, and this can lead to aging.
As we age, some of these pathways get cranked up, and some of them get turned down
…and this reduces longevity.
The next hallmark that we’re going to cover is mitochondrial dysfunction.
The mitochondria perform a host of functions within the cells, but their primary function is the production of ATP
…a molecule that stores chemical energy
and that is the energy source for 90% of the functions and processes that occur within the human body.
As we age, the mitochondrial population decreases
and individual mitochondria become less efficient at producing ATP
…both of which seriously impacts the amount of ATP available.
As supplies of ATP go down, we have less energy
and bodily functions start to slow down, or worse, function improperly.
This causes cellular damage and this damage accumulates over time.
It also leads to an increase in a type of cell death known as apoptosis.
The final hallmark in the compensatory category is cellular senescence,
and it’s an irreversible condition where the cells stop dividing and most of their cellular functions end.
Now, when most cells reach this state in their life cycle, they just die and are recycled.
But for some reason, senescent cells don’t die and they go on as a sort of zombie cell.
Over time, these cells can accumulate and cause a lot of bad things to happen.
They can cause surrounding cells to become senescent, they release pro-inflammatory cytokines,
they can reduce tissue repair and they can lead to other hallmarks of aging.
Now we get to the last category in the hallmarks of aging, and that’s the integrative hallmarks.
These are hallmarks that lead to functional decline and they’re downstream from the first two categories.
The first of these is stem cell exhaustion. All cells in the human body have the same DNA, or genetic code.
Cells are different and have different functions because various genes are either turned on or turned off.
This is called genetic expression.
This is the cell’s epigenetic settings and for most normal cells, this setting can’t be changed or altered.
But stem cells are different.
They can change their epigenetic settings, allowing most of them to become any type of cell in the body.
Stem cells are what allow the body to renew itself
and they're important for tissue repair, immune function, and blood cell production.
But as we age, stem cell activity becomes reduced, and this leads to aging
…particularly as tissue repair falls into decline.
And finally, we get to altered intracellular communication
…the final hallmark of aging and the last one in the integrative category.
Cells are constantly communicating with each other through the use of chemical messengers.
As we age, the cells increasingly produce inflammatory distress signals that cause damage to other tissues.
An example of this is the pro-inflammatory cytokines secreted by senescent cells.
This altered intracellular communication has two primary effects.
It causes chronic inflammation which inhibits the immune system
and it causes a hormone imbalance, leading to muscle wasting, bone loss and skin degradation.
As I mentioned at the beginning of this video,
I’m planning on doing separate videos on each of the 9 hallmarks of aging.
In those videos, I’ll be going into more detail about what each of them is, how the processes work,
how they start to malfunction, their causes and what therapies are available to treat them.
This is going to be a major undertaking,
and I’d like to hear from you guys if this is something that you’d like to see.
Now, I'll be interspersing videos on other topics in with them, and given how often I post videos,
this project could take 6 to 9 months.
So I’d really like to hear from you guys before I commit to such a large project.
If you’d like to download this infographic that outlines the 9 Hallmarks of Aging,
I’ve put a link to it in the description below.
And if you enjoyed this video and would like more, then seriously,
think about hitting that subscribe button and subscribing to this channel.
Hit the like button.
Thanks for watching, and I’ll see you next time.