Strengthening the Brigade: How Scientists Rejuvenated the Immune System of Aging Mice

Wednesday - April 3 2024, 00:53 UTC - 7 months ago

Scientists have found a way to restore the balance of the immune system in aging mice, making it act more like a youthful one. This could have implications for fighting age-related diseases such as dementia, stroke, and heart attacks. The treatment involves targeting a specific subpopulation of stem cells in the bone marrow using an antibody, which helps to eliminate chronic inflammation and boost overall immunity. The findings highlight the importance of blood stem cells in maintaining a healthy immune system and suggest potential strategies for preventing age-related diseases.

Our immune system is like a well-trained brigade. Each unit has a unique specialty. Some cells directly kill invading foes; others release protein "markers" to attract immune cell types to a target. Together, they’re a formidable force that fights off biological threats—both pathogens from outside the body and cancer or senescent "zombie" cells from within. With age, the camaraderie breaks down. Some units flare up, causing chronic inflammation that wreaks havoc in the brain and body .

These cells increase the risk of dementia, heart disease, and gradually sap muscles. Other units that battle novel pathogens—such as a new strain of flu—slowly dwindle, making it harder to ward off infections. All these cells come from a single source: a type of stem cell in bone marrow. This week, in a study published in Nature, scientists say they restored the balance between the units in aged mice, reverting their immune systems back to a youthful state .

Using an antibody, the team targeted a subpopulation of stem cells that eventually develops into the immune cells underlying chronic inflammation. The antibodies latched onto targets and rallied other immune cells to wipe them out. In elderly mice, the one-shot treatment reinvigorated their immune systems. When challenged with a vaccine, the mice generated a stronger immune response than non-treated peers and readily fought off later viral infections .

Rejuvenating the immune system isn’t just about tackling pathogens. An aged immune system increases the risk of common age-related medical problems, such as dementia, stroke, and heart attacks. "Eliminating the underlying drivers of aging is central to preventing several age-related diseases," wrote stem cell scientists Drs. Yasar Arfat Kasu and Robert Signer at the University of California, San Diego, who were not involved in the study .

The intervention "could thus have an outsized impact on enhancing immunity, reducing the incidence and severity of chronic inflammatory diseases and preventing blood disorders." Stem Cell Succession All blood cells arise from a single source: hematopoietic stem cells, or blood stem cells, that reside in bone marrow. Some of these stem cells eventually become "fighter" white blood cells, including killer T cells that—true to their name—directly destroy cancerous cells and infections .

Others become B cells that pump out antibodies to tag invaders for elimination. This unit of the immune system is dubbed "adaptive" because it can tackle new intruders the body has never seen. Still more blood stem cells transform into myriad other immune cell types—including those that literally eat their foes. These cells form the innate immune unit, which is present at birth and the first line of defense throughout our lifetime .

Unlike their adaptive comrades, which more precisely target invaders, the innate unit uses a "burn it all" strategy to fight off infections by increasing local inflammation. It's a double-edged sword. While useful in youth, with age the unit becomes dominant, causing chronic inflammation that gradually damages the body. The reason for this can be found in the immune system's distribution of labor .

Blood stem cells first spawn "progenitor" cells that can become either fighter adaptive or inflammatory innate units. If more units are needed on a specific front, some blood stem cells pool together to form "killed plated colony-forming cells" (KP-CFCs) that churn out only the needed group.