#469 Latest Research About Reversing Aging Cells - Dr Paul Robbins, PhD

Paul Robbins (0:00)

I think we're going to come up with different drugs and different cocktails of drugs that will show signs of non-reducing senescence, but actually using transcriptome, the lipidome, the metabolome, all the different omics make a cell look younger. So could you engineer our genome to carry variants that have been shown to lead to extend the lifespan in humans?

Siim Land (0:22)

Dr. Robbins, welcome to the show.

Paul Robbins (0:25)

Great, pleased to be here, Siim.

Siim Land (0:27)

Yeah, I'm happy to have you on the podcast. Now, many people might not be aware of you, but you're pretty known in the longevity field. So maybe you can give a short and brief introduction about your background and what is your main area of the research.

Paul Robbins (0:44)

Yeah, great. Yes. So I actually started in the gene therapy field. So my first job is assistant professor at University of Pittsburgh, focused on gene therapy for a variety of diseases. I ran a vector core facility in addition to running the Medical Medicine Institute. But as we're developing therapies for a number of different diseases, I started to realize that the root cause of many of these diseases were similar, and they seem to be things that change with aging. So I very quickly bought into this geroscience concept that the greatest risk factor for most diseases is the aging process. So when I moved to the Scripps Research Institute in Jupiter, Florida, we started to focus on ways to target aging therapeutically, choosing cellular senescence as the hallmark of aging, which we thought was the most drugable at the time, and this was more than a decade ago. Six and a half years ago, I moved to the University of Minnesota, where I'm the co-director of the Masonic Institute on the Biology of Aging and Metabolism, and we're very focused on cellular senescence, but a few other hallmarks of aging as targets to try to extend health span, not necessarily lifespan.

Siim Land (1:54)

Gotcha. Yeah. Senescence is synonymous to aging. And you mentioned one of the hallmarks of aging is cell senescence. So what is cell senescence in the human body and other organisms? What kind of a phenomenon is it and how does it relate to aging?

Paul Robbins (2:15)

Right. Great question. And so cellular senescence or its senescence cells, it's a cell fate. So this is what happens to almost any cell in your body if it acquires too much damage. So this could be genotoxic stress, it could be oxidative damage, it could be mechanical stress. And if these cells then are stimulated in the way that they don't like, what they do is they exit the cell cycle and they undergo what's known as cellular senescence. And what your body wants to do is get rid of these cells. So these senescent cells, in many cases, not all, start to release inflammatory factors. And this stimulates your immune system to come clear them. So Siim, at somebody of your young age, your immune system is probably clearing thousands or tens of thousands of senescent cells a day. It does it very effectively. But as we age and our immune system starts to fail, and you accumulate more cells, there are tips of balance where our immune system doesn't clear them.

And this leads to an increase in inflammation, but other adverse effects that are caused by this chronic accumulation of senescent cells. But senescence is thought to be an anti-tumor mechanism. So one of the ways that the cells are induced to enter a senescent cell state is by activation of an oncogene, a mutation in the gene or protein that drives cells to replicate. So when cells start to replicate when they're not supposed to, this senescent cell fate kicks on, cells enter this, exit the cell cycle, enter the state of cellular senescence, secrete these inflammatory cytokines, and the immune system clears them, and that reduce our risk of cancer. So senescence is a positive thing, but as we age and these cells accumulate, it can drive adverse pathologies and diseases related to aging.

Siim Land (4:06)

So every cell has its, I guess, expiration date or a lifespan, and one of the outcomes of that journey is the cells senescence.

Paul Robbins (4:18)

Well, I don't know if they all have necessarily a lifespan, if just if a cell, and this can be a fully differentiated non-dividing cell, such as a liver cell or a kidney cell or a brain cell, if they acquire so much damage that this cell fate then is stimulated and takes over. So, some cells never senesce other cells, if they have damage, will senesce. The other thing is that a senescence cell can drive neighboring cells or cells of the distance to enter a similar state because of these inflammatory factors.