The 1,25D 3 ‐MARRS receptor/PDIA3/ERp57 and lifespan

Using MRI on mice bearing a targeted knockout (KO) of the 1,25D 3 ‐MARRS receptor/PDIA3/ERp57 we found that they had decreased body fat relative to their littermate (LM) controls, a condition associated with increased lifespan. Others have found that lower body fat is correlated with decreased lipid droplets in intestinal cells that may be mediated by a factor secreted by germ cells (possibly estradiol). In a reducing environment estradiol competed for binding to the 1,25D 3 ‐MARRS receptor/PDIA3/ERp57. A consequence of this was that estradiol stimulated calcium uptake in enterocytes isolated from LM mice. In time course studies, lipid droplets increased in response to 1 nM estradiol from 1–5 D of culture, relative to corresponding controls, while at 6 and 7 D this steroid decreased lipid droplets. Enterocytes from LM or KOs incubated with estradiol for 1–4 D showed the hormone increased lipid droplets. Using the 4 D culture period, 1 and 10 nM estradiol significantly increased the number of lipid droplets in cells from LM mice by 40–60%, compared to equivalent conditions in KO mice. In assessing signal transduction pathways, the hormone increased phospho‐Akt levels, but no differences were observed in phospho‐mTORC1, or phospho‐S6K (although cells from chicks did exhibit a hormone‐mediated difference). Finally, the remaining mice (which had stopped reproducing) were allowed to die naturally and lifespan recorded. LM mice lived 687 ± 77 D (without an outlying value) while KO mice lived 740 D ± 80 D. These data suggest the 25D 3 ‐MARRS receptor/PDIA3/ERp57 may contribute to the length of lifespan in mammals. J. Cell. Biochem. 116: 380–385, 2015. © 2014 Wiley Periodicals, Inc.