Combating aging: Preliminary trials show just a single shot may be the key to youthfulness preservation

The physical aging process is commonly dreaded; not many look forward to the decline of their strength or increased susceptibility to various diseases. These natural side effects of aging seem inevitable, but a recent study regarding the development of a novel therapeutic mechanism reveals that this may not be the case. 

A team of researchers led by Corina Amor Vegas at the Cold Spring Harbor Lab recently discovered a life-altering treatment using engineered T-cells: white blood cells that play a central role in the immune system by attacking foreign substances. Incorporating these cells into laboratory mice increased their health spans by targeting cells that contribute to the physical decline associated with aging. 

The targeted cells are “senescent” cells, meaning they have stopped dividing despite existing in optimal growth conditions. In younger people, senescent cells often arise in wound healing to support tissue regrowth or when suppressing a tumor that consists of rapidly dividing cells. An active immune system can clear such cells to restore normal function, but the immune system weakens with age and cannot clear senescent cells as efficiently. Accumulation of these cells leads to pathologies associated with old age, such as decreased fitness and metabolic dysfunction, which can increase the risk of diabetes, stroke, or heart disease. 

The elimination of senescent cells can therefore decrease the risk of developing such age-related symptoms. Past research has shown that small-molecule drugs can target these cells and partially help reduce this risk, but they require constant administration and cannot target precise, well-defined senescent cell markers. Amor Vegas and her team discovered that the chimeric antigen receptor (CAR) T-cell, engineered to target a cell-surface protein specific to senescent cells, can be administered in a single-dose and provide lifelong treatment against such age-related disease.

The team found that the injection of aged mice with the CAR T-cells successfully aided in the elimination of senescent cells. This manifested in reduced physiological symptoms compared to the control. Treated mice showed lower inflammatory factors associated with old age and improved metabolic health, as indicated by reduced improved pancreatic cell function and glucose homeostasis. 

Researchers also injected young mice with CAR T-cells and discovered that such treatment has preventative effects as well; when the treated mice reached nine months, they experienced higher exercise capacity and, similar to those injected at an older age, limited metabolic decline compared to the control. The CAR T-cells both persisted and expanded over the mice’s lifespan, meaning that only a single treatment of CAR T-cells is necessary for lifetime effects. 

“Expanding the health span using T-cells lays a preliminary foundation for further discoveries that could unlock the secrets of slowing the entire process of aging, such as whether they can also expand longevity.”

Expanding the health span using T-cells lays a preliminary foundation for further discoveries that could unlock the secrets of slowing the entire process of aging, such as whether they can also expand longevity. At the very least, these cells have the potential to be a powerful therapeutic tool for the treatment and prevention of disorders associated with aging, significantly increasing well-being for a plethora of people worldwide.