Altered intercellular communications.
Sounds like the title to a sci-fi movie, but it's actually the name of one of the "Hallmarks of Aging."
And it’s key to a new field of study called “Regenerative Medicine,”
which is just what it sound like:
medical therapies that can regenerate new tissue.
And it’s a hallmark you’ll want to know about if you want to turn back the clock.
This is the second in my series on the “Hallmarks of Aging.”
Instead of working my way through the hallmarks in order, starting with the primary hallmarks,
then the compensatory and finally the integrative,
I’m doing them in the order that I need them…to provide background info on upcoming videos.
Altered intercellular communications is what’s called an “integrative” hallmark.
There are 3 categories of hallmarks,
first the primary hallmarks, which are interrelated hallmarks that are the foundational causes of aging.
Everything else stems from these.
Next come the compensatory, or response, hallmarks.
These are all caused as a response to the primary hallmarks, or as an attempt to compensate for them.
And finally, the integrative hallmarks.
These are functional declines that incorporate the first two hallmarks.
Since they’re downstream from them, therapies that target the first two categories
should have a beneficial effect on the integrative hallmarks.
But there are some things that we can do that can favorably impact this hallmark,
and we’ll get to those a little later in the video.
But first, we’re going to take a look at how intercellular communications work.
Intercellular communication is an intricate system of chemical signaling
that the cells use to communicate with one another…and it goes on all the time.
Cell release molecules that can travel through the circulatory system to distant cells,
and can then alter the function of those cells.
And changes in these signals can lead changes in cellular function, which is one of the definitions of aging.
And when these chemical signals start to run amok, things can go into a downward spiral pretty quickly.
Cellular behavior can affect the cellular environment, in the form of these chemical signals.
Changes in the cellular environment can in turn affect cellular behavior.
An example of this in action, and an example of how upstream hallmarks can impact integrative hallmarks,
is cellular senescence, which is a compensatory hallmark.
As some cells become senescent,
they release DNA-damaging chemicals known as “Reactive Oxygen Species”, or ROS.
They also release bioactive molecules called senescent-associated secretory phenotypes, or SASPs.
These include pro-inflammatory cytokines and chemokines, immunosuppressive chemicals,
tissue-damaging proteases and growth factors;
all contributing to tissue microenvironment alterations and loss of tissue homeostasis.
As a result, the signaling environment of chemical messages becomes more and more inflammatory…
causing chronic inflammation.
This inhibits the immune system.
It causes muscle wasting and bone loss, also known as sarcopenia and osteoporosis,
as well as other harmful effects.
This process has been called “inflammaging”, a term used to denote aging caused by chronic inflammation.
As SASPs alter the intercellular microenvironment,
they can encourage healthy cells in close proximity to also become senescent,
through what’s known as the “by-stander” effect.
And these new senescent cells also start secreting SASPs, causing a cascading effect.
Chronic inflammation leads to cells activating a chemical in their nucleus called NF-kB,
which stands for “Nuclear Factor kappa-light-chain-enhancer of activated B cells”.
Which is a mouthful for a protein the regulates inflammatory response.
But it also regulates the production of proteins, enzymes and other local signals known as cytokines.
It’s considered one of the master regulators of cellular activity,
and it’s increase can lead to harmful consequences.
Activation of NF-kB in the hypothalamus,
a region of the brain that is dedicated to maintaining normal bodily function,
has been shown to inhibit production of GnRH, also know as gonadotropin-releasing hormone.
A reduction of GnRH can contribute to bone fragility,
muscle weakness, skin degradation and other harmful effects associated with aging.
It can also lead to a decline in the production of testosterone.
So, altered intercellular communication can cause an increase in chronic inflammation,
as well as seriously mess with your hormones.
But, how does this chemical signaling thing work?
Well, one way that they work is when something called multivescular bodies,
or MVBs are formed by sort of budding out from the Golgi apparatus of the cell.
These MVBs contain a number of smaller vesicles that in turn contain a variety of different types of molecules,
such as proteins, DNA and RNA.
These MVBs migrate outwards and when they fuse with the cell membrane,
they then release these membrane-bound vesicles into the extracellular environment as EVs,
or extracellular vesicles.
These EVs can then travel to distant cells, which can then uptake the EVs through cellular receptors,
where they can then alter cellular function.
Now, this can be either good or bad.
Chemical signaling can degrade cellular function through inflammation,
but it can also improve cellular function, as in the case of exosomes.
OK, so what can we do that can have a positive impact on this particular hallmark,
suppressing the negative impacts like chronic inflammation and hormone modulation,
and improving the positive impacts?
Well, like I said earlier, one thing that you can do is to target the upstream hallmarks.
Since this particular hallmark is a result of the upstream ones,
taking care of them should also take care of this one…to some extent.
That’s the theory, anyway.
But there are some things that you can do to specifically target this particular hallmark.
Now, unfortunately, most of these strategies are not simple things…
like exercising more or taking a specific supplement.
A lot of these are therapies that you’re going to have to go to a doctor to obtain.
Now, having said that, the first thing is actually pretty simple, and that’s to improve your gut microbiome.
We have over 10,000 species of bacteria living in a symbiotic relationship with us,
outnumbering human cells ten to one.
And these bacteria produce signaling molecules, just like human cells.
So anything you can do to improve your gut microbiome, like taking probiotics and prebiotics,
will help these bacteria to send out positive chemical signals.
Now, the next thing may sound a little weird.
It’s been known for a while now that blood from young individuals can have a rejuvenating effect on the elderly…
at least in mice.
It was assumed that there was something in the young blood that had this effect,
but that was disproved in a study published in May of this year, in a journal called “Aging”.
Irina Conboy, a professor of bioengineering has authored a number of papers on this subject,
including the 2005 mice-joining study that started this whole thing off.
In 2016, they did a study in which they demonstrated that,
rather than young mouse blood rejuvenating old mice, old mouse blood in fact aged young mice.
In the most recent study, they discovered that there are aging molecules in old blood
that send chemical signals that are responsible for aging.
And here’s the interesting part.
They found that by extracting old blood, separating out the plasma,
diluting it with saline and albumin to remove many of the harmful, age-elevated factors,
and then re-infusing the mice with the diluted plasma
had the same rejuvenating effects on the old mice as the young blood in the co-joined mice.
So, it’s not that there are rejuvenating factors in young blood that kept the mice young
or rejuvenated the old mice,
but rather that there are aging factors in old blood,
and removing these aging factors from the old blood can have a rejuvenating effect on aging mice.
And hopefully, on humans as well.
Another therapy that will improve intercellular communication is exosome therapy.
Now, I’m going to be doing a video on this in the future, but in the meantime, here’s what you need to know.
Exosomes are an example of the membrane-bound, extracellular vesicles
that I was talking about a moment ago.
They contain protein, DNA and RNA,
and when they travel to distant cells and are absorbed by them, they can change the behavior of tate cell,
stimulating them to regenerate new tissue.
Exosomes are part of a new field of medicince called "Regenerative Medicine."
Regenerative medicine has been using stem cells to achieve regenerative effects,
but there’s some problems with stem cells.
They can take a long time to take effect, they can be rejected,
they can be inflammatory and they can cause an immunological effect.
But here’s the thing, stem cells achieve their effect through chemical signaling,
and they use exosomes as their chemical messengers.
Exosomes that are derived from stem cells have all the same benefits without many of the drawbacks.
They can’t be rejected, they don’t cause inflammation immunological effects, and the take effect immediately.
And because once they absorbed by the target cells, they cause the target cells to secrete more exosomes,
they can continue having an effect for up to 6 months or so.
Hope you enjoyed this video, thanks for sticking to the end.
If you’re interested in more videos on the “Hallmarks of Aging,” check out this one.
That’s it for me, I’m outta here.