Columbia University scientists restore the regenerative capacity of blood with the arthritis medication anakinra in old mice.
Approximately one trillion cells arise from our bone marrow daily. This is because our bone marrow contains the stem cells responsible for blood production. These hematopoietic stem cells (HSCs) give rise to all blood cells, including red blood cells, platelets, and immune cells (white blood cells). However, with age, our HSCs decline, leading to anemia, impaired immunity, and cancer.
“We know that bone tissue begins to degrade when people are in their 50s. What happens in middle age? asks Dr. Emmanuelle Passegué, the principal investigator of the latest study on blood aging. “Only by having a deep molecular understanding will it be possible to identify approaches that can truly delay aging.
In the study, published in Nature Cell Biology, researchers from Columbia University, UCSF, and Cambridge University report evidence to suggest that blood aging can be reversed by the arthritis medication, anakinra. Upon detailed examination, Mitchell and colleagues confirm that HSCs are hindered by inflammation. They also find that blood regeneration is disrupted in old mice in response to stress but can be improved with anakinra.
Within a localized niche, our bone marrow stores HSCs, which are capable of becoming all blood cell types, giving rise to new blood. Mitchell and colleagues showed that aging leads to inflammation of this niche in mice, causing impairments in HSCs. Furthermore, to determine how impaired HSCs and aged blood responds to stress, the researchers exposed mice to a chemotherapy drug called 5-fluorouracil (5-FU), which destroys bone marrow stem cells as they propagate.
Compared to young mice, old mice were far more sensitive to 5-FU, with a 50% reduction in survival, likely due to blood clotting. The old mice also had fewer red blood cells, a symptom of anemia, and decreased B immune cell production. The old mice also exhibited an increase in inflammatory molecules, including IL-1α and IL-1β. These results suggest that age-related inflammation of the HSC niche compromises blood regeneration.
To determine if reducing the inflammatory mediator IL-1 can reverse features of aging blood, Mitchell and colleagues treated mice with the IL-1 blocker anakinra for 14 days. This led to minimal changes in blood production and HSCs in aged mice. However, exposing the mice to 5-FU reduced IL-1α and IL-1β levels and improved blood production in old mice, including increased B cells and red blood cells. These results demonstrate that anakinra improves blood regeneration in old mice.
“An aging blood system, because it’s a vector for a lot of proteins, cytokines, and cells, has a lot of bad consequences for the organism,” says Dr. Passegué. “A 70-year-old with a 40-year-old blood system could have a longer healthspan, if not a longer lifespan.”
The findings of Mitchell and colleagues suggest that we can reverse blood aging by preventing inflammation, especially by using anti-inflammatory drugs. This supports the idea of inflammaging, which refers to the aging process being caused, or at least, largely due to chronic low-grade inflammation. Since our blood affects every cell in our body, stopping bone marrow inflammation and HSC impairments could have profound age-countering effects.
Model: 18- to 31-month-old C57BL/6 CD45.2 mice
Dosage: Intraperitoneal injection of 10 mg/kg/day anakinra for 14 days