June 17th, 2026
Thrombospondin-1 is a component of the senescence-associated secretory phenotype (SASP) produced by senescent cells. It has been shown in the past to induce blood-brain barrier dysfunction, but here researchers show that it also degrades mitochondrial function in macrophages, biasing those cells into the inflammatory M1 state. This in turn contributes to chronic inflammation and dysfunctional bone regeneration. The accumulation of senescent cells with age is known to be an important aspect of degenerative aging, and the SASP is known to change bystander cell behavior for the worse. There are likely countless mechanisms of this nature taking place in the aging body, all of which could be suppressed via reduction of the burden of senescent cells.
The aging bone marrow microenvironment is characterized by chronic low-grade inflammation ("inflammaging"), which disrupts skeletal homeostasis and impairs bone regeneration. However, the stromal-immune crosstalk mechanisms sustaining this pathological state remain poorly defined. Here, transcriptomic analysis identified thrombospondin-1 (Thbs1) as a key upregulated component of the senescence-associated secretory phenotype (SASP) in aged bone mesenchymal stromal cells (BMSCs).
