Now, onto cellular senescence which is sort of a result of this whole idea too. We’ll categorize
these different physiological traits as we summarize the lecture. But cellular senescence is definitely one
where we’re challenging the checks and balances of our cells. Cellular senescence by definition
is the stable arrest of the cell cycle associated with phenotypic changes. It’s a protective mechanism, right?
Recall that it is intended to prevent propagation of damaged cells and trigger their clearance
by the immune system. Cellular senescence is actually something that we need in order to have
a healthy life and healthy cells. Now, cellular senescence acts in a couple of different ways.
When we’re young, this is how it works. We see sporadic damage. You’re familiar with this mechanism.
Cellular senescence comes along and prevents propagation of bad cells or cells that don’t have
everything right in place, prevents their proliferation to produce tissues. However, if the cells
are undamaged or things get fixed then we can produce the right tissues. Now, this acts to prevent
cancer naturally because if we have DNA damage, we don’t want to proliferate those cells.
So, this is a mechanism of checks and balances to prevent against cancer. It allows us to age
more gracefully, let’s say because we’re not letting these damaged cells proliferate.
So, if we take care of ourselves, perhaps we can have our cell lines live a little bit longer.
When we consider cellular senescence in the aging cell, we actually see an increase in cellular senescence.
Keep in mind that cellular senescence means stalling of the cell cycle, right? So things that affect
cellular senescence are going to be increased damage, all the things that we’ve actually discussed
already, increased damage in the cells, decreased rates of repair, and decreased clearance of issues
of bad proteins inside the cell as well as decreased cell renewal are going to lend themselves
to an increasing rate of senescence or slowing of cell division. When we see slowed cell division,
naturally we’re going to start seeing a decrease in tissue function as well as an increase in inflammatory
responses in order to clear damaged cells. In addition to that, bringing us towards the next topic,
we see that there is stem cell exhaustion, so we run out of stem cells. As you can see, cellular senescence
is going to lead to tissues working less efficiently and thus are pro-aging in this sense.
Recall that cellular senescence is there in the healthy cell to block proliferation of damaged cells
so that we can have anti-aging effects and anti-cancer effects. But because we’re accumulating damage
that we’ve spoken about previously in this lecture, it leads to an increased rate of cellular senescence
which lends itself to aging. So, take a moment. Roll that around in your head a little bit. Perhaps, pull out
a piece of paper. Pause the video. See if you can write down the connection between the damages
that we’ve previously looked at, cellular senescence, and the outcome of aging. On that note,
let’s take a quick look at the stem cell exhaustion concept. Stem cell exhaustion is definitely associated
with aging, essentially stem cells, not only because of telomeres but run out of divisions.
When stem cells are exhausted, we start seeing that we might have myelodysplasia, so anemic
symptoms due to the myelodysplasia and production of blood cells and osteoporosis because we see
a decreased rate of fracture repair. There are no stem cells to regenerate the new tissues.
We might also see a decrease in repair of muscle fibers. So, you can see that especially in a whole aging
individual as their muscle tone becomes less and less. In addition to that, we can see decreased
intestinal function which leads itself in conjunction with nutrient sensing to a declined nutritional state
which is why it’s especially important to make sure older adults are getting plenty of the right nutrition.
All of this is an integrated consequence of so many of these other hallmarks. So in summary,
I want to consider these hallmarks in three different categories. Perhaps that will help you recall
what all of they are because clearly, they’re all interrelated and some lead to the others
and so on and so forth. So, let’s do that. Our primary hallmarks are actual hallmarks that cause damage
to the cells, so genomic instability, telomere attrition, epigenetic alterations, as well as loss of proteostasis.
Next, we have the category of antagonistic hallmarks. They’re not necessarily antagonistic in the way
of antagonistic but they are responses that happen due to the damage that’s accumulated in the cells.
So deregulated nutrient sensing is a result. Mitochondrial dysfunction can be a result
of some of the issues of primary hallmarks as well as the issue of cellular senescence, increased rates
of cellular senescence, decreased cell division. Then we have our final category which were the truly
integrative hallmarks which are the true culprits of the phenotype, so how aging actually manifests itself.
Because of stem cell exhaustion, we can no longer regenerate tissues. We see altered intercellular
communication which results in decreased communication between those tissues.
Hopefully, this slide makes a great summary for you of the different, nine different hallmarks of aging.
You can keep them color-coded in your mind and recall all of the different things
that account for cellular aging. I look forward to seeing you in the next lectures on aging
where we’ll be discussing some of the degenerations that we see in brain tissue.