CSHL scientists have found a way to reprogram T cells to fight aging. After using them to eliminate specific cells in mice, the scientists discovered they lived healthier lives and didn't develop aging-associated conditions like obesity and diabetes. Just one dose provided young mice with lifelong benefits and rejuvenated older mice.
The fountain of youth has eluded explorers for ages. It turns out the magic anti-aging elixir might have been inside us all along.
Cold Spring Harbor Laboratory (CSHL) Assistant Professor Corina Amor Vegas and colleagues have discovered that T cells can be reprogrammed to fight aging, so to speak. Given the right set of genetic modifications, these white blood cells can attack another group of cells known as senescent cells. These cells are thought to be responsible for many of the diseases we grapple with later in life.
Senescent cells are those that stop replicating. As we age, they build up in our bodies, resulting in harmful inflammation. While several drugs currently exist that can eliminate these cells, many must be taken repeatedly over time.
As an alternative, Amor Vegas and colleagues turned to a "living" drug called CAR (chimeric antigen receptor) T cells. They discovered CAR T cells could be manipulated to eliminate senescent cells in mice. As a result, the mice ended up living healthier lives. They had lower body weight, improved metabolism and glucose tolerance, and increased physical activity. All benefits came without any tissue damage or toxicity. Amor Vegas says:
"If we give it to aged mice, they rejuvenate. If we give it to young mice, they age slower. No other therapy right now can do this."
Perhaps the greatest power of CAR T cells is their longevity. The team found that just one dose at a young age can have lifelong effects. That single treatment can protect against conditions that commonly occur later in life, like obesity and diabetes. Amor Vegas explains:
"T cells have the ability to develop memory and persist in your body for really long periods, which is very different from a chemical drug. With CAR T cells, you have the potential of getting this one treatment, and then that's it. For chronic pathologies, that's a huge advantage. Think about patients who need treatment multiple times per day versus you get an infusion, and then you're good to go for multiple years."
CAR T cells have been used to treat a variety of blood cancers, receiving FDA approval for this purpose in 2017. But Amor Vegas is one of the first scientists to show that CAR T cells' medical potential goes even further than cancer.
Amor Vegas' lab is now investigating whether CAR T cells let mice live not only healthier but also longer. If so, society will be one mouse step closer to the coveted fountain of youth.
Citation
Amor, C., et al., "Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction", Nature Aging, January 24, 2024. DOI: 10.1038/s43587-023-00560-5
(Score: 2) by fraxinus-tree on Sunday January 28 2024, @02:29PM (4 children)
It is bad enough when random reasons make immune system kill your own cells, so let's try to train it to do so.
(Score: 1, Insightful) by Anonymous Coward on Sunday January 28 2024, @03:36PM (2 children)
Yeah, I don't think I'll be an early adopter of anything like this. But as the years go by, the temptation could certainly increase...
(Score: 2) by boltronics on Monday January 29 2024, @02:58AM (1 child)
I'll probably adopt it when I get to around 80 if it looks safe and popular enough. It depends on how my gaming backlog is going. Right now it's not looking great.
It's GNU/Linux dammit!
(Score: 2, Informative) by Anonymous Coward on Monday January 29 2024, @03:17PM
You'd probably need more than that for it to help for humans. It may work for mice because mice lifespan is for like 2-3 years. They don't have all the other mechanisms humans have that allow us to live to 80+.
That's probably not a problem when your oldest cells are 2-3 years old. But is likely to be a problem when very many of your important cells are 80+ years old and aged/senescent.
Imagine the problem like this: you have stem cells. The stem cells split and make other cells (for growth and replacement). The process of splitting can cause errors. There's DNA repair, but even DNA repair has its limits. To reduce the odds of cancer and other errors you limit the number of splits with the telomere thing (once the telomeres get too short, no more splitting). Yes it sucks that you can't get an infinite number of new cells, but that's a trade off to avoid getting too many cells that too wrong given the "messy method of cell replication".
You'd eventually get cells that are wrong, some suicide, some are killed but some survive - that's why as people get older, they lose hair, get white hair, spots on their skin, etc. But such errors don't kill the organism that fast.
Now imagine if you suddenly got rid of all the cells that weren't perfect in an 80 year old. Would that person still be able to stay alive? Imagine having an old worn out car, and removing all the parts that aren't perfectly good, will the car still be able to work after you do that?
See also: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588127/ [nih.gov]
The reason why some whales can live so long despite having tons more cells than we do and thus a LOT more cell splitting and replication, is because they have better repair mechanisms: https://www.sciencenews.org/article/bowhead-whales-cancer-dna-repair [sciencenews.org]
See also: https://www.scientificamerican.com/article/why-elephants-don-rsquo-t-get-cancer/ [scientificamerican.com]
So what you'd need is better repair, better detection and killing off of erroneous cells AND somehow getting the stem cells to produce more cells beyond their "normal limits". If you just increase the "strictness" and killing efficiency you might have a human that looks youthful for quite a while but then starts having difficulty producing enough new cells that meet the strict standards and dies.
https://www.newscientist.com/article/dn25458-blood-of-worlds-oldest-woman-hints-at-limits-of-life/ [newscientist.com]
See also: https://book.bionumbers.org/how-quickly-do-different-cells-in-the-body-replace-themselves/ [bionumbers.org]
(Score: 3, Interesting) by Beryllium Sphere (r) on Sunday January 28 2024, @07:11PM
Interestingly, another form of CAR T is showing promise for treating autoimmune disorders. https://www.nature.com/articles/d41586-024-00169-7 [nature.com]
I sure wouldn't be the first, but these are the days of miracle and wonder.
(Score: 3, Funny) by Mojibake Tengu on Sunday January 28 2024, @03:53PM
Yet the Thymus programming is limited for advanced spirit masters only. And vampires.
Rust programming language offends both my Intelligence and my Spirit.
(Score: 3, Insightful) by Adam on Sunday January 28 2024, @04:24PM
It would be difficult for me to watch test subjects get healthier and more youthful with potentially longer lives without considering quietly self administering.
(Score: 0) by Anonymous Coward on Sunday January 28 2024, @06:20PM (1 child)
Of the ass too, the worst kind.
(Score: 3, Funny) by istartedi on Sunday January 28 2024, @09:05PM
Fond memories of rooming with a med student when I was an undergrad. I once joked that he could be the first doctor to perform an asshole transplant, and he actually replied in all seriousness that if transplant surgery could restore what he called "sphincter tone", and restore control, it would be beneficial. I have no idea if this has ever been done, or if he went on to surgical residency; but if you're out there dude, I hope you get your chance some day.
Appended to the end of comments you post. Max: 120 chars.
(Score: 4, Interesting) by ElizabethGreene on Sunday January 28 2024, @09:03PM (4 children)
I'd be curious to know the mass of CAR T cells, specifically if they are light enough to be present in centrifugally separated plasma. That would help tie a bow on the question of why young-to-old plasma transfer seems to have anti-aging effect in mice, but filtration-separated plasma does not.
(Score: 1) by Guppy on Monday January 29 2024, @02:29AM (2 children)
I think there might have a misconception here, Chimeric Antigen Receptor T-cells are, pretty much by definition, artificial. The level of such cells in the population is zero, outside a small number of patients undergoing chemotherapy/immunotherapy.
(Score: 2) by ElizabethGreene on Monday January 29 2024, @03:50PM (1 child)
I did misunderstand; Thank you.
(Score: 2) by sjames on Monday January 29 2024, @04:35PM
But the question isn't entirely off base. It may be that something transferred in unfiltered young plasma performs a similar function but not as long. That's just speculation, but it raises questions that point to useful testing.
(Score: 1) by shrewdsheep on Monday January 29 2024, @08:54AM
By definition, plasma would be cell-free. White blood cells (buffy coat) would abut the plasma fraction using centrifugal fractionation, if that's what you are hinting at, implying that few white blood cells are likely to be present in plasma (https://en.wikipedia.org/wiki/Blood_fractionation).
(Score: 2) by Spamalope on Monday January 29 2024, @01:16AM (2 children)
Is this turning off defense against cancer metastasizing? That's appeared to be a function of some of the cell division limits.
(Score: 3, Informative) by deimtee on Monday January 29 2024, @08:35AM
You're thinking of telomeres. [genome.gov] They do set a cell division limit and are implicated in aging, but IMO they are a pretty shitty cancer control method.
Combine this therapy with telomere restoration and the results might be very interesting.
If you cough while drinking cheap red wine it really cleans out your sinuses.
(Score: 3, Informative) by sjames on Monday January 29 2024, @04:26PM
This is almost the opposite. It doesn't block senescence, it destroys the cells that reach senescence to get them out of the way.