Can We Reprogram Aging Through Mitochondria? | Dr. Stefan Isaac

Fantastic.

So let's connect the dots now.

So we basically are very interested and, um, focus the podcast on things like, uh, healthy aging and longevity.

Mitochondria seem to be the organelle du jour as far as people really being interested in how it may be connected to things like aging and longevity.

So could you tell us what maybe role mitochondria play, uh, not just in longevity, but as part of the aging process itself? So what happens as mitochondria go through this aging process?

Right.

So there's a lot of things, and it's, it's hard to know with a lot of these processes what is the cause versus what is the consequence.

And before I answer your question, and I think a lot of the problems that, that you have these feed-forward loops.

So something goes wrong, it causes other problems, and then that causes more things to go wrong.

And so then those boundaries of cause and consequence really start to break down.

Um, and I think especially with mitochondria, because they are so highly integrated into many, many cellular processes, um, and I think that's kind of why it's a mistake to just think about them as a powerhouse of the cell, because then that makes you think of every problem as an energy deficit problem, but you actually have a multitude of problems.

So mitochondria are definitely a very hot topic right now with aging, and, you know, some of the data are, that are out there, for example, are that when you use these, um, mutator mouse, this mutator mouse model, so basically it's an, it's a mutation in the enzyme that makes mitochondrial DNA.

And so when you make a lot of mistakes in this mitochondrial DNA, you see progeria-like, so prematurely, premature aging-like phenotypes.

And so of course-

So interesting

... it's, it's way above the burden what you see in, in, you know, aged humans, but that does link mitochondrial DNA damage to, um, aging phenotypes.

There's also, like, Hutchinson-Gilford progeria, which is actually a mutation in a nuclear protein, but you see mitochondrial, um, morphological defects and functional defects.

So there is this, we do observe this link between premature aging and mitochondrial dysfunction, but again, cause and consequence is a little blurred.

As it is with many things in the aging realm.

I think you mentioned something that I think is pretty, uh, interesting that maybe people may not, uh, completely appreciate.

I think people are familiar with what DNA is, and they know that they have DNA inside of all their cells, that it's the sort of blueprint or stuff of life that connects us to all living things.

But mitochondria have their own DNA.

Can you tell us a little bit about that and what are the consequences of, uh, mutations maybe occurring in your normal somatic DNA versus your mitochondrial DNA?

Yep.

So essentially, um, you know, you have these multiple compartments in your cell.