Genetically Modified CAR T Cells Eliminate Senescent Cells and Improve Health in Mice Study

Unique Points

• Senescent cells accumulate with age leading to a chronic pro-inflammatory milieu that leads to a range of age-related tissue pathologies.
• uPAR is upregulated on senescent cells, making it a potential target for elimination of these harmful cells.

Accuracy

No Contradictions at Time Of Publication

Deception (30%)

• The article states 'In contrast, CAR T cells are a form of cellular therapy that redirects T cell specificity toward cells expressing a specific cell-surface antigen11.' This statement implies that CAR T cells have the ability to specifically target senescent cells. However, there is no evidence presented in the article to support this claim.
• The article states 'ResultsuPAR is upregulated in physiological aging uPAR promotes remodeling of the extracellular matrix during fibrinolysis, wound healing and tumorigenesis13.' This statement implies that senescent cells are a major contributor to age-related metabolic dysfunction. However, there is no evidence presented in the article to support this claim.
• The article states 'We have shown that CAR T cells targeting the cell-surface protein uPAR, which is upregulated on senescent cells, can efficiently deplete senescent cells in young animals and reverse liver fibrosis.' This statement implies that CAR T cells are effective at eliminating senescent cells. However, there is no evidence presented in the article to support this claim.

Fallacies (80%)

• The article states that 'senolytic strategies have the potential to dramatically improve healthspan' but does not provide any evidence or research to support this claim. This is an example of a hasty generalization fallacy.

Bias (75%)

• > In physiological conditions in young individuals (for example, wound healing, tumor suppression), the SASP contributes to the recruitment of immune cells, whose role is to clear the senescent cells and facilitate restoration of tissue homeostasis3. However, during aging...

Site Conflicts Of Interest (50%)

• The study was funded by a company that produces senolytic CAR T cells. The authors declare no competing interests.

Author Conflicts Of Interest (50%)

Unique Points

• T cells can be genetically reprogrammed to target and eliminate senescent cells.
• A single treatment with these modified T cells offers long-term health benefits.
• This discovery expands the medical applications of CAR T cells beyond their current use in cancer therapy.

Accuracy

• Senescent cells are a stress response program characterized by stable cell cycle arrest and the production of the senescence-associated secretory phenotype (SASP), which includes pro-inflammatory cytokines and matrix remodeling enzymes.
• Most efforts to develop senolytic therapies have focused on small molecule drugs that target poorly defined molecular dependencies present in senescent cells and must be administered repeatedly over time.
• uPAR is upregulated in physiological aging uPAR promotes remodeling of the extracellular matrix during fibrinolysis, wound healing, and tumorigenesis.
• Senescent cells accumulate with age leading to a chronic pro-inflammatory milieu that leads to a range of age-related tissue pathologies.
• CAR T cells targeting uPAR can efficiently deplete senescent cells in young animals and reverse liver fibrosis.
• The study explores whether CAR T cells could safely and effectively eliminate senescent cells in aged mice and modulate healthspan.
• Senescent cell accumulation is a hallmark of aging, leading to tissue dysfunction, inflammation, metabolic decline and increased risk for age-related diseases.
• CAR T cells can be programmed to seek out and destroy senescent cells in vivo.
• The study shows that CAR T cell therapy could delay the onset of age-associated diseases by targeting senescent cells, which accumulate with aging.
• Senescent cell elimination is a promising strategy for modulating healthspan.

Deception (50%)

• The author is deceptive when they say that 'If we give it to aged mice, they rejuvenate. If we give it to young mice, they age slower.' This is a lie by omission because the article does not provide any evidence or data on how long the effects of CAR T cells last, or if there are any differences between young and old mice in terms of response to treatment.
• The author is deceptive when they say that 'Perhaps the greatest power of CAR T cells is their longevity.' This is a vague and exaggerated statement because it does not define what 'longevity' means in this context, or how it compares to other treatments. The article also does not address the potential drawbacks or limitations of using CAR T cells for aging-related diseases.
• The author is deceptive when they say that 'CAR T cells have been used to treat a variety of blood cancers, receiving FDA approval for this purpose in 2017.' This is a false statement because CAR T cells are not approved by the FDA for treating aging-related diseases, and their efficacy and safety for such purposes have not been proven. The article also does not mention any clinical trials or human studies that support this claim.
• The author is deceptive when they say that 'CAR 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.' This is a misleading statement because it implies that CAR T cells are more effective and longer-lasting than other treatments, without providing any comparison or evidence. The article also does not explain what 'memory' means in this context, or how it relates to the treatment of aging-related diseases.

Fallacies (85%)

• The fountain of youth has eluded explorers for ages.

Bias (85%)

• The article uses language that depicts CAR T cells as a panacea for age-related diseases. For example, it states '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.'
• The article uses language that depicts CAR T cells as superior to other therapies for aging-related diseases. For example, it states 'As an alternative, Amor Vegas and colleagues turned to a “living” drug called CAR (chimeric antigen receptor) T cells.'
• The article uses language that depicts senescent cells as harmful and responsible for many age-related health issues, which may not be entirely accurate or fair. For example, it states 'Senescent cells are those that stop replicating. As we age, they build up in our bodies, resulting in harmful inflammation.'
• The article uses language that depicts the discovery of CAR T cells as revolutionary. For example, it states 'This groundbreaking approach, offering long-term effects from a single treatment, could revolutionize treatments for age-related conditions like obesity and diabetes.'
• The article uses phrases such as 'magic anti-aging elixir' and 'fountain of youth' to sensationalize the findings. For example, it states '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.'

Site Conflicts Of Interest (100%)

None Found At Time Of Publication

Author Conflicts Of Interest (100%)

None Found At Time Of Publication

Unique Points

• Senescent cells accumulate more and more as years go by
• The CAR T cells could remove senescent cells which are responsible for many conditions and diseases associated with ageing such as obesity and diabetes.
• CAR T cell therapy acts like a prophylactic, staving off their decline into old age.

Accuracy

• The key to slowing ageing is hidden within the white blood cells known as T cells.
• Senescent cells accumulate more and more as years go by, building up harmful inflammation. The CAR T cells could remove them, thereby slowing the impacts of ageing.

Deception (50%)

• The title implies that this study has found a way to make people younger and live longer forever which is not true.
• The author claims that CAR T cells can remove senescent cells from our bodies and slow down aging but does not provide any evidence or scientific studies to support their claim.

Fallacies (85%)

• The key to slowing ageing lies within our bodies.

Bias (85%)

• CAR T cells have already been approved in the USA to tackle blood cancer.
• living drug
• The fountain of youth
• trick to anti-ageing lies within our bodies

Site Conflicts Of Interest (100%)

None Found At Time Of Publication

Author Conflicts Of Interest (0%)

None Found At Time Of Publication

Unique Points

• CAR T cells can be programmed to seek out and destroy senescent cells.
• Young mice treated with CAR T cells aged slower, had lower body weight, improved metabolism and glucose tolerance, increased physical activity without any tissue damage or toxicity. A single dose at a young age can have lifelong effects.
• CAR T cells have the ability to develop memory and persist in the body for long periods of time.
• Young mice treated with CAR T cells had protection from natural aging-associated conditions like obesity and diabetes.

Accuracy

• Senescent cells accumulate as we age and are responsible for many diseases later in life.

Deception (50%)

• The title implies that T cells are the fountain of youth when in fact they are a tool to fight aging.

Fallacies (85%)

• The author uses an appeal to authority by stating that CAR T cells have been used to treat a variety of blood cancers and received FDA approval for this purpose in 2017. However, the article does not provide any evidence or research on the effectiveness of CAR T cells for treating aging-related conditions like obesity and diabetes.
• The author uses inflammatory rhetoric by stating that senescent cells are responsible for harmful inflammation as we age, but this is a generalization and may not be true in all cases.

Bias (100%)

None Found At Time Of Publication

Site Conflicts Of Interest (50%)

• “living” drug called CAR (chimeric antigen receptor) T cells.
• ␵patients who need treatment multiple times per day versus you get an infusion, and then you␵re good to go for multiple years.
• The article discusses the potential of CAR T cells to treat age-related diseases and slow aging. The author has a financial interest in this topic as they work at Cold Spring Harbor Laboratory (CSHL), which is involved in research on senolytic CAR T cells.
• The article discusses the potential of senolytic CAR T cells to treat chronic pathologies.
• young mice treated with CAR T cells age slower
• young mice treated with CAR T cells age slower and have protection from natural aging-associated conditions like obesity and diabetes.

Author Conflicts Of Interest (50%)

• “living” drug called CAR (chimeric antigen receptor) T cells.
• One of the first scientists to show that CAR T cells medical potential goes even further than cancer.
• ␵patients who need treatment multiple times per day versus you get an infusion, and then you␵re good to go for multiple years.
• The article discusses the potential of CAR T cells to treat age-related diseases and slow aging. The author has a financial interest in this topic as they are an Assistant Professor at Cold Spring Harbor Laboratory (CSHL) which is involved in research on senolytic CAR T cells.
• The article discusses the potential of senolytic CAR T cells to treat chronic pathologies.
• young mice treated with CAR T cells age slower

Unique Points

• The study was conducted in mice and its results cannot be applied to humans.
• In the study, the researchers injected mice with CAR T cells that they genetically modified to seek out and attack senescent cells.
• > The protective effect of one treatment seemed to last about a year in the mice (lab mice typically live around two years).
• Unlike small molecules, CAR T cells only require that the target antigen is differentially expressed on target cells compared to normal tissues and have the potential to persist and mediate their potent effects for years after single administration.
• > The key to slowing ageing is hidden within the white blood cells known as T cells.

Accuracy

No Contradictions at Time Of Publication

Deception (30%)

• The study was conducted in mice and its results, while tantalizing, cannot be applied to humans.

Fallacies (75%)

Bias (75%)

• — an obsession that captures the hearts and minds of scientists, billionaires and wellness fanatics alike.
• Crucially, the mice seemed to experience no adverse affects from the CAR T cell therapy.
• •If we give it to aged mice, they rejuvenate.’ If we give it to young mice, they age slower.
• remarkable
• tantalizing pathway for future research

Site Conflicts Of Interest (50%)

• .
• ‘Rejuvenates’ old mice.
• The protective effect of one treatment of the CAR-T cell therapy seemed to last about a year in the mice (lab mice typically live around two years).

Author Conflicts Of Interest (50%)