Sirtuin 1

We also have it working on sirtuins and PARPs.

So in human stem cells, VLAN raised SIRT1 gene expression six times and protein 8.2 times in young cells.

In aging cells, it cut PARP1 by 2.1 times and 5.3 times and PARP2 by 2.1 times and 4.7 times.

That's a very fancy scientific jargon way of saying we have these sirtuins and PARPs, which are these longevity molecules in the body.

I think that could do really well with skin.

We'll see if that comes along at some point in the future.

It raises SIRT1 6X in gene expression and 8.2X in protein.

It lowers the NAD-hungry PARPs.

Pears are very good.

So now, what other agent helps you to express your SIRT1 better? It's omega-3.

Now you know why I'm so anal about omega-3 levels.

They need to be.

Like which ones?

The big ones are the sirtuins, specifically SIRT1 through SIRT7, and the PARP enzymes.

You can think of sirtuins like the cellular maintenance crew.

They regulate inflammation, they manage your circadian rhythms, and they organize your DNA.

They looked at hematocrit.

And with the SIRT1-floxed CD-CRE recipient, they showed a markedly longer survival and improved kidney function.

So, SIRT, FLOX, CD, CREE recipients exhibit donor-specific tolerance, even though these were allografts.

And they rejected, nevertheless, a third-party C3H cardiac allograft.

So the C57-BL6 recipients of the BALB-C renal allografts were further treated with the inhibitor for SIRT1.

And what did they demonstrate? What was the presentation after that? Improved survival and renal function.

Now, that occurred at low concentrations of the inhibitor, but not at the higher concentration, 10X.

Remember? Probably.

You have other enzymes that use cyclic ADP, and that is also associated with calcium mobilization, as I just said.

So that means when you look at individual enzymatic activity, SIRT1, for example, will inhibit PARP1.

You'll remember this.

I mentioned I take a lecture two or three.

The other group did time restricted feeding, same time fasted, but they skipped breakfast and had lunch and dinner and ate between 2:00 PM and 8:00 PM.

And then they tracked different metrics, uh, insulin, glucose, but they also tracked autophagy, which is really hard to track, but they did it in the lab looking at the LC3H protein, and then they also tracked, uh, their sirtuin genes which are their longevity genes, their sert- uh, SIRT1 genes.

And what they found was that the group that was eating breakfast and lunch and skipping dinner versus the other group had 22% more autophagy activated and 10% more of their sirtuins activated.

And it made sense because we're designed to have most of our calories during the day.

In other words, you measure sirtuin 1 in the blood.

How does that measurement, that quantification of sirtuin 1 in the s- in serum relate to the amount of sirtuin 1 biological activity, remember it requires NAD, say, in a neuron or a microglia or an oligodendrocyte or an astrocyte? Do you see? Because that's what you really wanna know, 'cause that's where the sirtuin 1 seems to be playing a major role, for example, in neurodegeneration, also DNA repair, et cetera, et cetera, et cetera.

That doesn't mean that you can't find a way to link serum SIRT1 with intracellular, intranuclear sirtuin 1, 'cause you should be able to if you do the right kinds of studies.

[coughs] But you cannot assume that.

That can't be a premise when you're generating hypothetical deductions for arguments, arguments to generate experimental designs to, to carry out work to be able to study it.

And what they think that means is that sirtuin 1 is linked perhaps then to Parkinson's, because remember this was all induced using that MPTP.

So what they did is they increased the expression sirtuin 1 in the animal by an inducible promoter in the midbrain.

And they used, again, classical adenovirus-associated viruses, AAV SIRT1 type of construct, and they examined its potential role in Parkinson's disease.

Now, there are seven sirtuins, and they have various enzymatic activities and therefore physiological functions, and they're all expressed in mammals, including humans.

So SIRT1, SIRT6, and SIRT7, those isoforms of these histone deacetylases, they localize to the nucleus.

And they seem to be the most relevant in DNA damage repair.

As their depletion, when we deplete them, for example, using short hairpin RNA, causes growth retardation, a defective DNA damage repair system using all the repair mechanisms, such as base excision and mismatch repair, And therefore, because of a defective DDR, what happens is there is premature aging.

Remember the protein I delivered to you, the phosphorylated protein that was associated with the phospho-linacetal kinase-like kinase? Remember that? Yeah.

Yeah.

that SIRT1 is going to associate with the gamma H2X.

And when it does that, remember that protein complex, it will deacetylate the XPA, the NBS, and the Ku70 proteins.