Cell senescence, when stressed cells can no longer divide to make new cells, is considered a factor in aging and in some diseases. As your body ages, increasing amounts of cells enter into a state of senescence. Senolytic drugs as anti-aging drugs are a promising approach to remove senescent cells, but researchers are still trying to figure out the role of cellular senescence and different ways to approach it. Researchers at the University of California, San Francisco (UCSF), report they have discovered how immune cells naturally clear the body of senescent cells. Their new findings in mice may lead to new strategies and approaches to treating age-related chronic diseases with immunotherapy.
The study was published in the journal Med in a paper titled, “Invariant natural killer T cells coordinate removal of senescent cells.”
“The accumulation of senescent cells within tissues can drive the progression of diseases,” wrote the researchers. “While removal of senescent cells with senolytic drugs has emerged as a promising therapeutic approach, the ubiquitous target of these drugs makes clinical applications challenging.”
Immune cells known as invariant Natural Killer T (iNKT) cells function as a surveillance system, eliminating cells such as senescent cells. However, iNKT cells become less active with age and factors that contribute to chronic disease.
The researchers started to investigate different ways to stimulate this natural surveillance system that offers an alternative to senolytic drugs.
“Using iNKT-targeted therapy can piggyback on their exquisite, built-in specificity,” explained Anil Bhushan, PhD, a professor of medicine at UCSF in the Diabetes Center and senior author of the study.
The scientists discovered they could remove senescent cells by using lipid antigens to activate iNKT cells. Researchers observed improvements in mice with diet-induced obesity. Their blood glucose levels improved, and mice with lung fibrosis had fewer damaged cells.
“I think this is a potential immune therapy for senescence and fibrosis,” noted Mallar Bhattacharya, MD, an associate professor of medicine at UCSF and an author of the study. “It’s a fairly well-tolerated therapy, and we just have to get around dosing and trials.”
“…Taken together along with the results presented here, these considerations suggest that specific activation of surveillance responses by iNKT cells provides a rationale for developing the next generation of approaches to eliminate inflammatory senescent cells associated with chronic diseases,” concluded the researchers.
Their results provide the first evidence that iNKT cells can eliminate senescent cells in these two distinct models where tissue dysfunction is dependent on the accumulation of senescent cells.