Senescent cells are those that aren’t dividing anymore but refuse to die. They’re the primary drivers behind the physical signs of getting older. In a new study, scientists at the University of California San Francisco (UCSF) have found a way to reinvigorate immune cells to clear out better these defunct cells contributing to the aging process. The new approach may lead to new ways of treating age-related chronic diseases as a sort of anti-aging immunotherapy.
The immune cells employed for this treatment are known as invariant Natural Killer T (iNKT) cells. They function as a surveillance system in a healthy state, eliminating cells the body senses as foreign – including senescent cells because they have irreparable DNA damage.
However, as we age, the immune system (particularly the iNKT cells) naturally begins to lose its effectiveness at destroying these freeloaders more and more over time. As a result, the senescent cells start to build up in our bodies, leading to the symptoms of aging and contributing to its associated diseases.
In the new UCSF study, the researchers investigated how to recharge the immune system to bring iNKT cells out of retirement. The team discovered that they could activate the iNKT cells using lipid antigens. This, in turn, reduced the number of senescent cells.
The iNKT cells are an especially appealing drug target mainly thanks to two attributes:
- The receptor that activates iNKT cells doesn’t appear on any other cell in the body, so the therapy can be particular. All iNKT cells have this receptor, and since other cells don’t, they can all be primed without also activating other kinds of immune cells.
- The iNKT cells will naturally settle into a dormant state after a period of activity because they function within a natural negative feedback loop, preventing the treatment from running too wild.
Anil Bhushan, Ph.D., the senior author of the paper and a professor of medicine at UCSF in the Diabetes Center, said:
Using iNKT-targeted therapy can piggyback on their exquisite, built-in specificity.
The researchers tested the treatment in mice with obesity and lung fibrosis – two different health conditions which increase senescent cells’ buildup. The mice with diet-induced obesity saw an improvement in blood glucose levels after the treatment. The mice with lung fibrosis had fewer damaged cells and also lived longer. In both groups, senescent cell numbers fell compared to controls.
Mallar Bhattacharya, MD, a study author and an associate professor of medicine at UCSF who treats lung disease patients, said:
I think this is a potential immune therapy for senescence and fibrosis. It’s a fairly well-tolerated therapy, and we have to get around dosing and trials. The results presented for iNKT cells in a mouse model of lung fibrosis offer hope for a potentially fatal disease that often leads to lung transplants. Further tests in human cells in culture showed that iNKT cells should also wipe out senescent cells in our bodies.
A spinoff company by the team is currently working toward verifying these findings through human testing, with an eye towards trials in the next few years.
Other techniques scientists have come up with in recent years to combat aging include using stem cells, using a specific enzyme that fixes DNA damage, and putting young mouse plasma into old mice.
