The immune system declines with age for a range of reasons. The thymus atrophies, reducing the supply of new T cells; persistent infection by cytomegalovirus causes cells to become uselessly specialized rather than ready to tackle new threats; and the hematopoietic stem cells responsible for generating immune cells become damaged, inactive, and dysfunctional. One of these forms of dysfunction is that hematopoietic stem cells begin to generate too many myeloid cells and too few lymphoid cells, the so-called myeloid skew.

The cause of this skewing in cell production is much debated, but researchers have found that chronic inflammation plays a role. Naturally, nowadays whenever inflammation appears to be an important aspect of any age-related dysfunction, attention turns towards senescent cells. Lingering senescent cells accumulate with age in all tissues, and secrete a potent mix of signals that rouses the immune system into an inflammatory state. It seems likely that they are an important part of the problem when it comes to the myloid skew in the hematopoietic stem cell population.

Why do senescent cells accumulate with age? Cells become senescent in great numbers throughout life, but only later do they linger to a significant degree. Near all are destroyed, either by their own programmed cell death processes, or by the immune system, called into action by the inflammatory signaling of the senescent cells. One reason for a greater number of lingering senescent cells in later life is that the immune system declines and falters in destroying errant cells. Thus, like many issues in aging, the relationship between cellular senescence and immune decline is a circular one; these two processes start off very slowly, but feed one other and accelerate as time passes and damage mounts.

Aged marrow macrophages expand platelet-biased hematopoietic stem cells via Interleukin1B