As you've probably been told tons of times in biology classes,
your genome tells each of your cells what type of a cell it is and what its job is,
but it's been known for a while now that this is not the whole story.
After all, every last cell in your body has the exact same set of genes,
so how is it possible that brain cells, for example, look nothing like muscle cells and do very different jobs?
The answer is, it's complicated, ridiculously so,
and it has important implications for human health and, you guessed it, aging.
Epigenetics is defined as the changes to the traits of an organism that are not caused by alterations to its genetic code;
rather, alterations happen on top of the genetic code, at least metaphorically,
and, indeed, that's what the Greek prefix "epi" stands for.
There are different types of epigenetic changes,
but, loosely speaking, they can all be imagined as the state change of a switch that can turn genes on and off.
As we've seen in our episode about genomic instability, genes encode for proteins,
but the protein encoded by a gene is produced only if the gene is expressed—that is, when it's switched on.
These gene switches are referred to as epigenome, which, unlike the genome, is not supposed to stay put;
rather, it can and does change, depending on a variety of circumstances.
For example, changes in gene expression are common during physiological development,
when unspecialized cells need to turn into specific tissue, such as heart or liver.
External and environmental factors can also influence gene expression;
smoking, for example, can flip genes on and off, and generally not in a good way,
as if smoking ever did anything good for you, and so can chronic stress.
Different types of switches can activate or deactivate genes.
DNA methylation is one way to turn genes off,
and it happens when the cell places a chemical called a methyl group onto a segment of the DNA.
Genetic code is read by a microscopic molecular machine called polymerase, which zips along the strand.
When a methyl group is placed on top of a gene within the strand,
this can prevent polymerase from accessing and reading the gene.
Another switch that involves attaching a chemical group is histone acetylation,
which is kind of the reverse of DNA methylation.
DNA is generally wound around a myriad of tiny spools called histones.
Acetylation happens when the cell places an acetyl group on a histone,
which has the effect of loosening the DNA coils around the spool,
allowing the polymerase to more easily access the genes than it could before acetylation.
The sort of beads-on-a-string structure we've described thus far may sound complicated enough as it is, but it gets worse.
The ensemble of DNA and histones folds on itself into a sort of spaghetti-like tangle,
with some portions being more tight and others being more loose.
The loose portions, called euchromatin, are the "active" part of the genome of a cell,
which is the part that can be expressed to make proteins,
whereas the tight parts, called heterochromatin, are silent.
The correct folding of DNA into active and inactive parts is crucially important for the functioning of cells;
euchromatin and heterochromatin are different in different cell types,
which means that cells of a given type have the same active portion of DNA,
which encode specifically for the proteins that are needed by cells of that type.
However, anything in biology that can go wrong generally tends to do so,
and it has been observed that, over time, the neatly organized compartmentalization of euchromatin and heterochromatin becomes not so neat anymore;
genes that were supposed to be silenced become active, and vice versa, causing cells to malfunction.
Some progeroid syndromes, conditions that look a lot like aging, like Werner Syndrome and Hutchinson–Gilford progeria syndrome,
present abnormalities in these organization mechanisms,
which reinforces the view that improper division between euchromatin and heterochromatin might play a role in cellular aging.
Aging seems to be accompanied by all kinds of epigenetic alterations that switch on genes that should be switched off, and vice versa,
and they appear to drive other hallmarks of aging, like cell senescence and mitochondrial dysfunction.
This may sound pretty bad, but don't despair yet; hopefully, we might be able to sort out this mess.
Remember that, unlike your genome, your epigenome can and does change;
this means that it may be possible to eliminate epigenetic alterations and return your epigenome to a healthy state,
kinda like hitting the reset switch to revert back to manufacturer settings.
As a matter of fact, this has already been done—well, in mice, not people, but we gotta start somewhere.
Scientists at the Salk Institute managed to reset the epigenome of mice suffering from progeria
by exposing them to a cocktail of four very special chemicals called Yamanaka factors.
Originally created by Prof. Shinya Yamanaka in 2006,
this cocktail is capable of turning specialized cells back into unspecialized stem cells:
essentially, Yamanaka factors make cells forget what their job and identity is.
However, while this is very useful as a means of creating stem cells,
turning all your cells back into stem cells isn't very advisable,
because they would no longer have any idea what they're supposed to do.
Still, given that the procedure turns specialized cells back into stem cells,
you might suspect that this somehow rejuvenates them,
and, in fact, that's exactly what was proved by Salk Institute scientists in 2016.
Salk researchers administered the Yamanaka factors to cells from mice with progeria, but only for a short period;
the result was that the cells' epigenetics were reset back to a younger state,
but the cells didn't forget their identity or job; they just had a younger epigenetic profile.
The researchers took this a step further and tried this same technique in live progeroid mice;
compared to the non-treated controls, treated mice lived 30% longer and showed improvements in the tissues of different organs,
such as the stomach, spleen, kidney, and skin, as well as improved vascular and cardiac activity;
the scientists also observed improved pancreatic function as well as better muscular regenerative capacity in the mice exposed to the Yamanaka factors.
There's definitely reasons to be enthusiastic for these results,
but let's keep in mind that they were observed in mice with artificially induced aging, not in people;
there is potential, but we're still some way before being able to do the same in humans.
In any case, we'll keep an eye on this area of research, and we'll let you know about future developments.
Thank you very much for watching this episode of X10, and thank you for liking and sharing this video.
If you have any questions to ask or simply want to show your appreciation for the video, leave a comment below.
Speaking of appreciation, we greatly appreciate the boundless generosity of the Lifespan Heroes,
the people who keep our boat afloat with their donations.
Without them, nothing that LEAF does would be possible, so, we thank all the Lifespan Heroes,
and we thank you if you're joining them.
To learn more about all things rejuvenation, don't forget to visit youtube.com/lifespanio and subscribe.
