Can Old Stem Cells Be Made Young Again?

Most of us think of ageing as wear and tear. Joints creak, skin thins, recovery takes longer, and we put it down to mileage. It feels like something that happens to the whole body at once, slowly and without a single cause.

Dr M. Carolina Florian has spent her career testing a less fatalistic idea. What if a big part of ageing comes down to a small population of cells losing their edge? And what if those cells could be nudged back into shape?

On Wednesday 28 October she brought that question to Growth Lab LIVE in Barcelona, in a talk called The Science of Anti-Aging: How to Hack Your Immune System. It was one of the most close-to-the-bench sessions we've run, and the room was properly gripped.

Why blood stem cells matter

Deep in your bone marrow sits a tiny reserve of blood stem cells. Every day they produce billions of new cells: the red cells that carry oxygen, and the white cells that make up your immune system. They are the factory behind your defences.

As we get older, that factory changes. Old blood stem cells regenerate less well, and the immune cells they make skew towards the kind that drive chronic inflammation. That shift is linked to weaker responses to infection and vaccines, and to a higher risk of blood cancers. Fix the stem cells, the thinking goes, and you might fix a lot downstream.

It also matters closer to home. Spain has one of the oldest populations in Europe, and Barcelona is no exception. The question of how to stay well for longer, rather than just live longer, is not abstract here.

The physics of an old cell

The most striking part of the evening was Carolina's walk through her lab's latest work, published this year in Nature Aging. It turns out an ageing stem cell isn't only a chemistry problem. It's partly a mechanical one.

The nucleus of a cell, where its DNA is stored, has physical properties: how stiff it is, how it holds its shape, how tightly the genetic material inside is packed. Carolina's team found that in old blood stem cells those mechanics go wrong, and that a protein called RhoA sits at the centre of it. When they briefly treated old stem cells with a drug that targets this pathway, the cells started behaving like younger ones again.

In her own words:

"We have revealed a novel nuclear bio-mechanical pathway in [blood stem cells]. Aging impairs nuclear mechanics, which decreases the capacity of old [blood stem cells] to regenerate the blood. A brief pharmacological treatment to improve the nuclear mechanics of old [blood stem cells] improved the function of these stem cells and their capacity to regenerate the hematopoietic system. Overall, we demonstrated that stem cell aging can be explained and targeted to rejuvenate [their] function."

That last line is the bit worth sitting with. Ageing here isn't a vague decline. It has a mechanism you can describe, and a mechanism you can describe is one you can try to fix.

Younger cells, longer lives (in mice, for now)

The RhoA work builds on more than a decade of research from Carolina and her collaborators. Earlier studies focused on a related protein, Cdc42, which also runs too hot in old blood stem cells. Calming it down with a drug rejuvenated the cells.

The results went further than healthier blood. Her team has rejuvenated aged blood stem cells in mice, and those mice lived longer. Old mice treated to dampen Cdc42 lived longer and had lower levels of inflammatory signals in their blood. In another study, transplanting rejuvenated stem cells extended the lifespan of aged mice with weakened immune systems.

The obvious next question is whether the same holds in people. That's where the lab is heading, with human blood stem cells as the next step. Encouragingly, earlier work has already shown that ageing human blood stem cells show the same Cdc42 changes seen in mice.

What we took home

  • Ageing has mechanisms, not just mileage. Some of the decline we feel can be traced to specific changes in specific cells.

  • Your immune system ages from the bone marrow up. Weaker defences and creeping inflammation start with the stem cells that build them.

  • Cells have physics. How stiff and well organised a nucleus is can decide whether a stem cell still does its job.

  • Be curious, and patient. Rejuvenating stem cells works in mice. Human studies are the next step, so treat anyone selling it in a bottle today with healthy suspicion.

Want to go further?

The most readable starting point is Carolina's own explainer, Rejuvenating haematopoietic stem cells to extend health and lifespan in Open Access Government. Two more project summaries are available here and here.

For the science itself, she recommends:

  • Mejía-Ramírez et al. (2026). Targeting RhoA nuclear mechanoactivity rejuvenates aged hematopoietic stem cells. Nature Aging.

  • Andersson, Mejía-Ramírez & Florian (2025). Haematopoietic ageing in health and lifespan. Nature Cell Biology.

  • Matteini, Montserrat-Vazquez & Florian (2024). Rejuvenating aged stem cells: therapeutic strategies to extend health and lifespan. FEBS Letters.

  • Montserrat-Vazquez et al. (2022). Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice. npj Regenerative Medicine.

  • Florian et al. (2020). Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female mice. Aging Cell.

About the speaker

Dr M. Carolina Florian is an ICREA Research Professor and leads the Stem Cell Aging group at IDIBELL in Barcelona. Her lab studies why our stem cells lose the ability to regenerate tissue as we age, and whether that decline can be reversed. She trained in Milan and at the University of Ulm in Germany, where she led her own group before moving to Barcelona in 2018. Her work has been featured in Nature and funded by the European Commission and Fundación "la Caixa".

Join us next time

Growth Lab LIVE runs every week in Barcelona. Small rooms, proper researchers, drinks after. See what's coming up and grab a ticket at growth-lab.live, and follow @growthlablive for recaps like this one.

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