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UCSF study demonstrates how immune cells could be used to alleviate age-related diseases

May 18, 2021

A new study has identified a potential immune therapy for senescence and fibrosis.
Scientists experimented with mice to see whether the body’s natural surveillance system could be stimulated to tackle a key hallmark of aging.
The research showed that activating a specific type of immune cells could help target and destroy senescent cells that underly aging and multiple chronic diseases.

New research carried out by scientists from the University of California San Francisco (UCSF) has demonstrated how some types of immune cells could be activated to damage senescent cells. The research was supported by a grant from NIH and the UCSF Diabetes Center Funds, and published in Med on May 2021. Senescent cells are usually beneficial in many ways, but their steady accumulation with aging paves the way for a myriad of aging diseases. Current interventions for removing senescent cells include the use of senolytics. These are a class of drugs that selectively eliminate senescent cells, thus alleviating the negative chronic effects of these cells. While the list of senolytic drugs and compounds has been extensively growing, there are concerns over their unknown but potentially dangerous side effects. The UCSF team investigated whether the body’s own natural surveillance system could be stimulated to do the same job — thus clear senescence without any side effects. Invariant Natural Killer T (iNKT) is a type of immune cells that targets and eliminates cells the body has identified as foreign. This includes senescent cells that have irreparable DNA damage but are still alive. INKT cells, however, become less active with age, leading to a decreased capacity to do their job. The researchers targeted a specific receptor that is unique to this specific type of immune cells. “Using iNKT targeted therapy can piggyback on their exquisite, built-in specificity,” said Anil Bhushan, a professor of medicine at UCSF and a senior study author. In mice experiments, lipid antigens were used to activate iNKT cells. The researchers then used two disease models in which senescent cells accumulate to test whether activation of iNKT cells could help eliminate senescent cells. Mice treated with diet-induced obesity showed improved levels of blood glucose levels. A group of mice that had lung fibrosis also seemed to suffer fewer damaged cells and showed an improved lifespan. These findings offer hope for the treatment of lung fibrosis, a disease that is characterized by damage and scarring of lung tissue and that could necessitate a lung transplant or even turn out fatal. “I think this is a potential immune therapy for senescence and fibrosis. It’s a fairly well-tolerated therapy, and we just have to get around dosing and trials,” said Mallar Bhattacharya, an associate professor of medicine at UCSF and one of the study’s authors. While more work needs to be done, this study clearly demonstrates that uncovering the senolytic capacity of tissue-resident iNKT cells could pave the way for anti-senescence therapies that target aging and alleviate a wide variety of diseases.

References: https://www.longevity.technology/researchers-find-mechanism-that-clears-senescent-cells/

UCSF study demonstrates how immune cells could be used to alleviate age-related diseases

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