Biological aging at the cellular level. Over the long term, this is what really causes
us to grow old and age. Though out all of human history, there hasn’t been a damn
thing that anybody could do about that. But in the last couple of decades, some amazing
advances have been made in the field of longevity, and we’re finally coming to an understanding
of what causes aging. And today, we’re going to examine the top 12 theories on the causes
of cellular aging.
This is Lance, and welcome to today’s video. I started this channel to share what I’ve
learned in my quest to turn back the clock on aging. If you enjoy this content, then hit
the subscribe button below. And also leave a comment and hit the like button.
Today we’re taking on cellular aging, and we’re going to be examining the top 12 theories
on the causes of biological aging at the cellular level. In the rest of the videos in this series,
we’ll be doing a deep dive into some of the more important ones and looking at them
in more detail. We’ll also be looking at some things that you can do, right now, to
slow them down. I posted a link to the first video in this series in the description below.
And as I post the rest of the videos in this series, I’ll be adding links to those videos
as well.
So, let me start off with a caveat. These 12 theories are in no particular order, because
there’s no consensus on which are the most important. Also, in the interests of time,
this is going to be a high level discussion. If you want more detail on three of them, along
with tips on what you can do to slow them down, check out the other videos in this series.
So…the first thing we’re going to talk
about is genome damage, or damage to our DNA. Corruption of the DNA takes two forms, damage
to the DNA, such as double- and single-strand breaks, which can be recognized by enzymes
and repaired; and mutations of the base sequence, which cannot be recognized by enzymes and
cannot be repaired. This leads to aging in a couple of ways. First, damaged DNA activates
DNA-repairing proteins called PARPs, which can exhaust supplies of NAD+, a molecule necessary
for supplying energy for a number of anti-aging processes. Also, corrupted DNA can lead to
an accumulation of dead or senescent cells, or dysfunctioning cells, both of which contribute
to aging.
Next up is telomere shortening. Telomeres are caps on the ends of the chromosomes which
protect the DNA from damage. With each cell division, these caps get shorter, until after
about 50 divisions, there’s nothing left to protects the DNA, and the cell then becomes
senescent…which leads to aging.
In third place is the field of epigenetics, which is the study of mechanisms that manage
the expression of genes and how many of these mechanisms decline with age. The term “expression”
in this case refers to the state of the gene…whether it’s turned on or off, whether it’s activated
or not. As these mechanisms decline with age, genes get activated incorrectly…which can
lead to aging.
Next is unfolded protein response, or mis-folded proteins. Proteins are long or short chains
of amino acids, that are folded into very specific and effective shapes. Proteins function
by getting into the correct shape. If proteins are unfolded, or mis-folded, then they either
malfunction…or don’t function at all. A build-up of these proteins is a major factor
in aging, especially in many age-related neuro-degenerative diseases.
Then there’s mitochondrial dysfunction.
Now this is not well understood. Mitochondria, as you may recall from high school biology
class, are organelles that are contained within the cells, and they’re responsible for cell
respiration and the cycling of ATP. ATP is what all of the nutrients that we consume
are turned into, and it’s the energy source that fuels every cell in our body, with the
exception of the brain. Mitochondria also have their own DNA, called mtDNA, but age-related
mitochondrial dysfunction can happen without significant damage or mutations of mtDNA.
Cell-mitochondria communication is one possible source of this dysfunction…but whatever
the source, it leads to aging.
Another cause of aging is cell senescence, which is when the functioning of aging cells
goes into decline. They stop dividing and they change activity and they can begin secreting
inflammatory molecules. Although the number of senescent cells can be quite small within
the human body, the damage they do can be profound and wide spread. And as they accumulate
over time, this damage can become more and more pronounced…and aging occurs.
OK, we’re halfway through. You know, if you find this type of content interesting,
and you’d like me to do more, or if you find it super boring and your having a hard
time staying awake, leave a comment below and let me know…either way.
OK, number 7. Stem cell exhaustion. Stem cells
are undifferentiated cells, meaning that they belong to no specific organ or tissue type,
but they can develop into very specific cell types…and there are many different types
of stem cells in the human body. Stem cells are what allow for the renewal of cells within
an organ. And as we age, stem cells become exhausted, due to DNA damage or overexpression
of proteins that block the cellular cycle. And stem cell exhaustion is one of the primary
causes of aging.
Next up is glycation, which is when sugar molecules in the bloodstream bind to proteins
and fats, resulting in harmful molecules called “advanced glycation end products.” Also
know as AGEs. While AGEs can impact the whole body, they have a particularly nasty effect
on skin. AGEs can cause both collagen and elastin to become discolored, weak and less
supple. And this can show up on the skin’s surface as wrinkles, sagging and a loss of
radiance…all symptoms of aging.
Number 9 is the AMPK pathway. Remember earlier, when I was talking about ATP, the universal
energy source. When ATP releases it’s energy, the ATP molecule is converted into a molecule called AMP.
Rising levels of AMP
and declining levels of ATP cause the activation of an enzyme called AMPK.
Activated AMPK promotes the rapid, efficient release of energy, with little energy storage as fat,
resulting in low blood sugar and fat levels, increased insulin sensitivity and a low risk
of heart disease, diabetes and other metabolic disorders. It also promotes the steady renewal
of cellular components, is critical to the immune system and reduces inflammation. But,
like everything else, AMPK levels decrease sharply with age, these processes then decline,
and this leads to aging.
Then there’s the damage caused by chronic inflammation and a declining immune system.
While acute inflammation can be a good thing, fighting off infections and helping to heal
wounds, chronic, systemic, and low-grade inflammation is complicated process where our bodies can
release pro-imflammatory signals, like cytokines and reactive oxygen species…and these substances
cause oxidative damage to our cells and tissues. As we age, our immune systems also go into
decline, make us more susceptible to chronic diseases. The thalamus, a gland that is responsible
for the creation of new T-cells, a major component of the immune system, goes into decline as
we age, slowing converting most of it’s active tissue into fat. Chronic inflammation
and a declining immune systems are considered my many to be a leading, if not the primary,
cause of aging.
At number 11 is the mTor pathway, which also involves the HGH/IGF-1 axis. This pathway
is the master regulator of anabolic metabolism, which is the process where new tissue is built.
mTOR regulates cell growth, proliferation, mortality, and survival, it regulates proteins
synthesis, autophagy and transcription. mTOR is activated by insulin-like growth factor
1, a derivative of human growth hormone, and it senses amino acids, becoming most active
in an environment of nutrient abundance. And here’s the thing about mTOR…it’s great
for growth, but bad for lifespans. Think about how rapid growth, like in insects and mice,
are associated with short lifespans. But slow growth, like with elephants and whales, is
associated with long lifespans. So with the mTOR pathway, it’s a trade-off. You can
have a lot of growth, or a long lifespan, but not both.
12 And finally, at number 12, are the sirtuins,
which are 7 genes that manage DNA repair. They’re actually nicknamed “the longevity
genes” because of the critical role that they play in many functions that influence
the aging process. They regulate mitochondrial biogenesis, they stimulate apoptosis and autophagy,
they inhibit inflammation, they stimulate signaling between the nucleus and the mitochondria
and between the hypothalamus and fat tissue. And three of them are involved in the repair
of DNA. And they can only function in the presence of NAD+, which declines with age…as
does the production of sirtuins. And guess what? That can lead to aging.
OK, finished! We got through it all. We’ve taken a high level view of the top 12 theories
on the causes of biological aging at the cellular level. Now, while some of these are being
researched, with therapies getting closer and closer every day, some of these theories
have resulted in interventions that you can implement today. And we’ll be looking at
some of those in greater detail in the rest of the videos in this series…along with
the accompanying treatments.
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And as always, thank you so much for watching.