Reprogrammed T cells can eliminate senescent cells, new research shows

Researchers have discovered that T cells, a type of white blood cells, can be reprogrammed to seek out and destroy senescent cells.

Longevity.Technology: As we age, senescent cells – often called zombie cells because they fail to die when they should – build up in our bodies as we age. They encourage other cells to become senescent and emit a toxic cocktail of chemicals called SASP, which promotes harmful, chronic inflammation. While several drugs currently exist that can eliminate these cells, many must be taken repeatedly over time.

As an alternative, a research team headed up by Cold Spring Harbor Laboratory (CSHL) Assistant Professor Corina Amor Vegas turned to CAR (chimeric antigen receptor) T cells. They discovered CAR T cells could be manipulated to eliminate senescent cells in mice, and as a result, the mice ended up with an improved healthspan. They had lower body weight, improved metabolism and glucose tolerance, and increased physical activity – and all the benefits came without any tissue damage or toxicity [1].

“If we give it to aged mice, they rejuvenate,” says Amor Vegas. “If we give it to young mice, they age slower. No other therapy right now can do this [2].”

One of the most interesting results is the longevity of the therapy; 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.

“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,” Amor Vegas explains. “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 [2].”

While CAR T cells have been used to treat a variety of blood cancers, receiving FDA approval for this purpose in 2017, this research shows that CAR T cells’ medical potential goes beyond cancer and has exciting longevity potential. The next step for Amor Vegas’ lab is to investigate whether CAR T cell therapy improves mice lifespan as well as healthspan.

As David Sinclair tweeted yesterday: “Imagine a single treatment that protects from aging, for life … it’s exciting to imagine a future where aging is a treatable disease.”

Image credit: Amor Vegas lab/Cold Spring Harbor Laboratory.
Image shows healthy pancreatic tissue samples from an old mouse treated with CAR T cells as a young pup.

[1] https://www.nature.com/articles/s43587-023-00560-5
[2] https://www.cshl.edu/the-fountain-of-youth-is-a-t-cell/