I’ve talked about the 9 Hallmarks of Aging a lot on this channel. But those
hallmarks might not be the whole story. In this video, we’re diving into 6 more
proposed hallmarks that could redefine our understanding of what it means to grow older.
In 2013, a Longevity researcher by the name of Dr. Carlos Otin-Lopez, published a paper
in which he proposed nine hallmarks of aging. In the decade since, after a lot of discussion and
controversy and debate, most scientists and researchers have accepted those 9 hallmarks.
I've talked before about the hallmarks of aging, a lot. In fact, I did a whole series on each of
the nine hallmarks of aging, plus an additional Hallmark that’s been suggested. But, like I said,
this generated a lot of conversations about hallmarks of aging, and as a result, a lot
of researchers and scientists have put forward their own suggestions for new hallmarks of aging.
Now, before I begin, I want to remind you guys that I've got an online course titled
“An Introduction to Longevity,” that will drop in a month or two.
If you'd like to become part of the Founders Group and enroll at a reduced rate,
then click on this link up here, or in the description below, and leave your email
address. I'll send you an email when the course is about to launch and I'm opening enrollment.
All right, before we dive in, let's do a quick review of the original 9 hallmarks. First up is
genomic instability, which is basically changes to the architecture of our DNA, of our genome,
particularly breaks in the strands of our DNA. Next is telomere attrition,
which is the erosion of the protective caps at the ends of our chromosomes called telomeres.
The third hallmark is epigenetic alterations. Basically, these are age-associated changes
that can lead to a remodeling of how and which genes get expressed.
Next, comes loss of proteostasis, which can lead to miss folded proteins and protein aggregation's.
Deregulated nutrient sensing can result from modern diets that are never lacking in nutrients.
Mitochondrial dysfunction is when the power houses of our cells stop producing as much energy as they
once did. Cellular senescence is when cells that are supposed to have died remain metabolically
active, spewing out toxins that can induce neighboring cells to become senescent themselves.
As we age, stem cells gradually accumulate so much damage that they cross the
threshold and become non-viable, leading to stem cell exhaustion,
the eighth Hallmark. Finally, we have altered intercellular communication,
which is a disruption in the chemical messaging that goes on between cells.
Now, in his original paper, Professor Otin-Lopez suggested that for a process to qualify as a
Hallmark, it should pass three criteria. It should be observed during normal aging.
If the condition worsens it should accelerate the aging process. And finally, if therapeutic
interventions can eliminate the worsening of the condition, aging biomarkers should be reversed.
In the decade since the first study was published, several additional processes or conditions have
been observed that seem to meet these criteria, and have been suggested as additional hallmarks
of aging. In fact, the authors of the original study led by Professor Otin-Lopez have published
a new paper, titled “Hallmarks of Aging: An Expanding Universe.” In it, they suggest
adding 3 new hallmarks to the list: Disabled Macroautophagy, Dysbiosis and Inflammation.
Now, other researchers have suggested other hallmarks, and a couple of them
seem very similar to a couple in the new paper. Compromised autophagy seems very similar to
disabled macroautophagy and Microbiome disturbance sounds like just another way of saying disbiosis.
Other suggestions for new hallmarks include altered mechanical properties,
cellular enlargement, and splicing dysregulation.
So, in today's video, I thought we’d take a look at all of these new, suggested hallmarks. In the
future, I’ll be doing a video on each of these for my ongoing series on the hallmarks of aging,
but today we’ll be taking a very high-level view where I’ll cover all of them very quickly.
Let's start off with the three suggestions from the new paper by the original authors of
the hallmarks of aging. The first of these new hallmarks is called “Disabled Macroautophagy,”
which I'm guessing is very similar to another new hallmark suggested by other researchers
called “Compromised Autophagy.” This was originally rolled in with loss of Proteostasis,
but it was recognized that autophagy is a process all on its own. Autophagy is a process
that happens inside of the cell when nutrients are scarce. Damaged proteins and organelles,
like the mitochondria, are broken down and recycled. This can lead to a renewal of the cell.
But's been observed in several different studies that autophagy becomes more compromised as we age.
It’s also been observed that dysfunction of autophagy shortens lifespans in test animals
and that restoration of autophagy seems to have the opposite effect,
extending both lifespans and healthspans in these animals.
The second new hallmark to be suggested is a condition known as “Dysbiosis". Other researchers
have suggested the name “Microbiome Disturbance,” but I’m guessing it's the same thing.
Alterations in the gut microbiome are both a cause and a consequence of aging.
These alterations are often brought about by changes in lifestyle,
which in turn can result from changing diet. Poor dental health and moving into
assisted living facilities are just a couple of factors that can result in changes to the diet.
But dysbiosis can also be brought about by loss of G.I. tract motility,
antibiotic therapies and long-term use of NSAIDs.
Dysbiosis can lead to an increased risk of infections, inflammation, and frailty.
Since the link between the gut microbiota and brain health has been recognized for
a while now, dysbiosis can also lead to problems with cognition.
It's interesting that “Inflammation" is now being suggested as a new hallmark. Inflammation results
from damages and aberrations that can result from the other hallmarks and was originally
part the hallmark known as altered intercellular communication. The role that systemic inflammation
plays in the aging process is so well established that it has its own name: inflammaging.
Researchers felt that the far-reaching effects of inflammation make it worthy of its own hallmark.
Another suggested hallmark is called “Altered Mechanical Properties.” This includes changes
to both the intracellular and the extracellular architecture and function. Some examples of
intracellular problems include changes to the lamina, the nuclear envelope that protects DNA,
and mechanical changes that can impede the mobility of fibroblasts and immune cells.
The most well-known extracellular change is the cross-linking of collagen through glycation. This
results in the loss of tissue elasticity and it changes how cells behave. It’s been called
the “Stiffening of the Extracellular Matrix” end it was suggested as an additional hallmark
several years ago. In fact I did a video on this suggested Hallmark back in Oct of 2021.
"Cellular Enlargement" is another proposed hallmark. It's been down for some time now
that sells invest heavily in regulating their size. It's not been known why. Recent studies
have shown that when cells become enlarged, aging is accelerated. For example, once a cell enters
a state of senescence, the production of new cellular material leads to cellular enlargement.
But a recent study observed that using Rapamycin to inhibit cellular enlargement not only reduced
cell size but also prevented cells from losing cell function and becoming senescence.
Finally, there's something called “Splicing Dysregulation." Now, this is different from
genomic instability, which refers to the DNA itself, and from epigenetic alterations,
which refer to the methylation of DNA. Splicing dysregulation refers to the
splicing process that builds RNA out of DNA and it's known to become impaired as we age.
OK, so, those are the processes or conditions that have been suggested as additional hallmarks
of aging. If you'd like to know more about the original nine hallmarks of aging as a whole,
or if you'd like to learn about each of them individually, then I suggest you watch this
playlist on the hallmarks of aging. That's it for me, I'm outta here. Catch ya next time.