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T cells can now be reprogrammed to slow down and reverse aging

Researchers from Cold Spring Harbor Laboratory have found that T cells, a type of white blood cell, can be genetically reprogrammed to combat aging. 

This innovative approach targets senescent cells, which cease to replicate and accumulate in our bodies as we age, causing harmful inflammation and contributing to age-related diseases.

Senescent cells

“During aging, the combination of increased tissue damage and decreased function of the immune system leads to the accumulation of senescent cells, thereby generating a chronic pro-inflammatory milieu that leads to a range of age-related tissue pathologies,” wrote the authors.

“As such, senolytic strategies to eliminate senescent cells from aged tissues have the potential to dramatically improve healthspan.”

T cell therapy

The study, led by Assistant Professor Corina Amor Vegas, utilized a technique known as CAR (chimeric antigen receptor) T cell therapy.

This “living” drug is already known for its effectiveness in treating certain blood cancers, having received FDA approval in 2017. 

However, Amor Vegas and her team are the first to demonstrate its potential beyond cancer treatment, showing its remarkable ability to rejuvenate and slow down aging in mice.

The results observed in mice were significant. They displayed a reduction in body weight, enhanced metabolism and glucose tolerance, and increased physical activity, all without any tissue damage or toxicity. 

“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,” said Amor Vegas.

Long-lasting effects 

A notable feature of CAR T cell therapy is its long-lasting effects. Unlike many drugs that require ongoing administration, a single dose of CAR T cells can provide lifelong benefits.

This is especially advantageous for chronic conditions such as 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 explained.

“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.”

Ongoing therapy research

The team is now investigating whether CAR T cell therapy can not only improve health but also extend lifespan in mice.

This research could represent a significant step towards unlocking the secrets of the elusive fountain of youth.

“Studies using genetic or pharmacological approaches to senolysis have been equivocal as to whether elimination of senescent cells will significantly extend longevity. Our current studies are not sufficiently powered to draw conclusions on longevity at this stage,” wrote the study authors.

“As senescent cells contribute to a range of age-related tissue pathologies, studying the impact of senolysis in aged animals provides an opportunity to interrogate multiple comorbidities under similar conditions.”

“Future studies will evaluate the potential of uPAR CAR T cells (or other senolytic cell therapies) in additional aging and related tissue-damage pathologies, the latter disease contexts providing a more likely starting point for clinical implementation.”

More about T cells

As discussed above, T cells, or T lymphocytes, are a type of white blood cell, forming a key part of the adaptive immune system.

They originate in the bone marrow and mature in the thymus, hence the name ‘T’. These cells are adept at identifying and destroying infected or abnormal cells in the body.

T cells, often overshadowed by the more commonly mentioned antibodies, are essential in our body’s relentless fight against infections and diseases.

Types of T cells

T cells come in various types, each with a unique function:

Helper (Th cells): These cells are the commanders of the immune system. They recognize foreign antigens and activate other immune cells by releasing cytokines.

Cytotoxic (Tc cells): These are the assassins of the immune system. They directly attack and kill virus-infected cells and cancer cells.

Regulatory (Treg cells): These cells are the peacekeepers. They help modulate the immune response, preventing autoimmune diseases.

Memory: These are the sentinels, providing long-lasting immunity by remembering past infections.

Functioning of T cells

T cells operate through a sophisticated mechanism. They use their T cell receptors (TCRs) to recognize specific antigens presented by MHC (Major Histocompatibility Complex) molecules on the surface of other cells.

This recognition triggers a series of immune responses, tailored to the type of threat faced.

Helper: They interact with antigen-presenting cells and, upon activation, secrete cytokines to stimulate other immune cells, including B cells and cytotoxic T cells.

Cytotoxic: These cells bind to infected or abnormal cells and release toxic substances like perforin and granzymes, which induce cell death.

Regulatory: They maintain immune tolerance by suppressing overactive immune cells, thus preventing damage to healthy tissues.

Memory: Upon re-exposure to the same antigen, these cells quickly expand and mount a more effective and rapid response.

Used in medical research

T cells are also front-runners in medical research. In cancer therapy, as discussed previously in this article, CAR-T cell therapy genetically modifies a patient’s T cells to better recognize and attack cancer cells.

This approach has shown promising results, particularly in certain types of leukemia and lymphoma.

In summary, T cells are indispensable to our immune system, offering a sophisticated defense mechanism against a multitude of threats.

From direct combat with infected cells to orchestrating the broader immune response, these cells are vital in maintaining our health.

Understanding and harnessing the power of T cells opens up remarkable possibilities in treating diseases, particularly those that have long evaded effective therapies.

The study is published in the journal Nature Aging.


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