The 1,25D3 -MARRS receptor/PDIA3/ERp57 and lifespan

Area of Science:

• Endocrinology
• Molecular Biology
• Gerontology

Background:

• Lower body fat is linked to increased lifespan.
• Estradiol may mediate lipid droplet changes in intestinal cells.
• The 1,25D3-MARRS receptor (PDIA3/ERp57) interacts with estradiol.

Purpose of the Study:

• To investigate the role of the 1,25D3-MARRS receptor (PDIA3/ERp57) in body fat regulation and lifespan.
• To explore estradiol's effect on lipid droplets and calcium uptake in intestinal cells.
• To determine the impact of the receptor knockout on mouse lifespan.

Main Methods:

• Generated mice with a targeted knockout (KO) of the 1,25D3-MARRS receptor/PDIA3/ERp57.
• Utilized MRI to assess body fat in KO and littermate (LM) control mice.
• Performed in vitro studies on enterocytes to analyze lipid droplets, calcium uptake, and signaling pathways in response to estradiol.
• Recorded lifespan of KO and LM mice until natural death.

Main Results:

• KO mice exhibited significantly decreased body fat compared to LM controls.
• Estradiol increased lipid droplets in enterocytes from both LM and KO mice, with a more pronounced effect in LM mice.
• Estradiol stimulated calcium uptake in enterocytes from LM mice.
• KO mice demonstrated a longer lifespan (740 ± 80 days) compared to LM mice (687 ± 77 days).

Conclusions:

• The 1,25D3-MARRS receptor (PDIA3/ERp57) plays a role in regulating body fat and influences lifespan in mammals.
• Estradiol's interaction with this receptor affects intestinal cell lipid metabolism and calcium transport.
• Targeting this receptor pathway may offer novel strategies for lifespan extension.