DEL-1 is an Endogenous Senolytic Protein that Inhibits Senescence-Associated Bone Loss

Area of Science:

• Gerontology
• Cell Biology
• Biochemistry

Background:

• Senescent cells, including bone marrow mesenchymal stromal cells (BM-MSCs), accumulate in the bone microenvironment, contributing to age-related bone degeneration.
• The expression of Developmental endothelial locus-1 (DEL-1), a secreted protein, declines with aging.

Purpose of the Study:

• To investigate the role of DEL-1 as an endogenous senolytic protein in clearing senescent BM-MSCs.
• To explore the therapeutic potential of DEL-1 in preventing senescence-associated bone loss and other age-related conditions.

Main Methods:

• Investigated the DEL-1 pathway involving β3 integrin/CD73/adenosine/p38 MAPK/BCL-2 in senescent BM-MSC apoptosis.
• Utilized DEL-1-deficient mice and mice with endothelial-specific DEL-1 overexpression (EC-Del1).
• Administered DEL-1 or a DEL-1-inducing macrolide to assess effects on senescence markers and bone loss.

Main Results:

• DEL-1 promotes apoptosis of senescent BM-MSCs via a specific molecular pathway, leading to their clearance by macrophages.
• DEL-1 deficiency exacerbates bone loss, while DEL-1 overexpression diminishes it.
• DEL-1 administration reduced senescence markers and reversed aging-related periodontitis.

Conclusions:

• DEL-1 functions as an endogenous senolytic protein capable of clearing senescent BM-MSCs.
• DEL-1 holds potential as a therapeutic agent to prevent senescent cell accumulation and treat age-related bone loss and periodontitis.