Youth and Time, John William Godward, 1901 (public domain)
For Signal’s annual blog carnival this year, we were asked to consider David Sinclair’s recent comments in the New York Times where he said “Aging is far more reversible than we thought.” As someone who has dedicated the better part of the last 20 years to studying stem cells in the context of healthy aging and disease, it was difficult to turn down the opportunity. For decades, the fantasies associated with the regenerative potential of stem cells have fuelled research into how we might deliver on statements such as the one above, a sort of naïve quest for eternal youth.
Perhaps the most dramatic (and also slightly science-fiction) example of old cells and tissues being “rejuvenated” by exposure to young cells came with a fleet of studies that explored the physical linking of circulatory systems of old and young mice (something called “heterochronic parabiosis”). A number of research groups across the world took advantage of this model system to demonstrate aspects of rejuvenation of particular tissues (e.g., muscles) or cell types (e.g., blood stem cells). Whether these changes were being driven by the exposure to various proteins and secreted factors that exist in circulation or the blood cells themselves was explored and both were found to contribute to aspects of rejuvenation.
More commonly and less ethically charged, other researchers have invested considerable effort into characterizing the molecular profiles of old versus young cell fractions to identify the genes or pathways linked to the core biology of being “functionally young”. Once identified, these factors could be tested by isolating cells from young or aged animals to try and rejuvenate them in vitro before re-infusing them back into the organism. One of the more recent and dramatic examples of this came from Segel et al., in 2019 who showed that rat neural cells could be rejuvenated on bioengineered scaffolds of different stiffnesses, demonstrating that such cellular manipulation was not limited to external molecules but could also be driven by physical and mechanical cues.
Another method explored by researchers is to use information gained from these rejuvenation studies to identify and test molecules that could be directly assessed in organisms. One potent example of this came from the work of the late Paul Frenette and colleagues where it was shown that sympathomimetics (drugs that stimulate the production of sympathetic nerves) could rejuvenate aspects of the aged adult bone marrow and better support blood forming cells in old animals.
As readers can probably imagine, especially those following the cellular reprogramming field, these are but a few of the incredible tales from researchers who have succeeded in rejuvenating various tissues and cell types of our bodies. Naturally, this inspires thoughts of bringing such therapies or treatments to market, but, as with most scientific research, the path to clinic is not so simple.
Despite tantalizing demonstrations of individual cell or tissue rejuvenation, advocates of the “fountain of youth” style off-the-shelf anti-aging agents are in for a long and hard road ahead. This is largely because the vast majority of research efforts are taken in highly controlled settings, studying individual cell types or tissues and measuring very specific cardinal properties of those cells rather than taking a wholistic approach to the impact of a particular treatment on the organ system or body at large.
Yes, we can pull an individual cell backwards in time and, yes, we can sometimes make an individual organ function a little better by giving it a boost with rejuvenating factors, but are scientists close to “reversing aging” in a way that might appreciably extend human lifespan across the population using simple single agents? Probably not. I think I’d keep my money on good old fashioned healthy lifestyle advice and keep stem cell therapies in the armamentarium for specific degenerative disorders or cell-replacement strategies where individual cells and tissues are impacted.
My blog is just one of many covering this topic as part of Signal’s sixth annual blog carnival. Please click here to read what other bloggers think about this.
David Kent
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