UC San Francisco Scientists Finds New Mechanisms that Eliminates senescent cells

Scientists are learning how immune cells naturally clear the body of defunct or senescent cells that contribute to aging and many chronic diseases. By Understanding this process many new ways of treating age-related chronic diseases with immunotherapy.In a healthy state, these immune cells are known as invariant Natural Killer T cells which function as a surveillance system, eliminating cells the body senses as foreign, including senescent cells, which have irreparable DNA damage. The invariant Natural Killer T cells become less active with age and other factors like obesity that contribute to chronic disease.

The scientists of San Francisco started finding ways to stimulate this natural surveillance system and offered an alternative to senolytic therapies, which to date have been the primary approach to removing senescent cells. It could be a boon to a field that has struggled with how to systemically administer these analytics without serious side effects.The invariant Natural Killer T cells have two attributes that make them appealing drug targets. First, they have the same receptor, which does not appear on any other cell in the body, so they can be primed without also activating other types of immune cells. Second, they operate within a natural negative feedback loop that returns them to a dormant state after a period of activity.

Anil Bhushan, PhD, a professor of medicine at UCSF in the Diabetes Center and senior author of the paper said that using this inverted Natural Killer T cells therapy can piggyback on their exquisite, built-in specificity.  Scientists also found they could eliminate senescent cells by using lipid antigens to activate inverted Natural T cells. When they treated mice with diet-induced obesity, their blood glucose levels improved, while mice with lung fibrosis had fewer damaged cells, and they also lived longer.

Mallar Bhattacharya, MD, associate professor of medicine at UCSF who treats patients with lung disease and is an author of the paper, added that the results presented for Inverted Natural T cells in a mouse model of lung fibrosis offer hope for a potentially fatal disease that often leads to lung transplants. Bhattacharya also added his thoughts on this potential immune therapy for senescence and fibrosis. It’s a fairly well-tolerated therapy, and we just have to get around dosing and trials.