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Marcozzi, S.

Publications and source records attributed to Marcozzi, S..

2 recordsLinked to original sources

Photographic age gap is associated with frailty and predicts survival in laboratory mice

Ageing studies in mice need biomarkers that are cheap, non-invasive and repeatable. We asked how much of a mouse's age can be read from an ordinary photograph, and whether the part that cannot be explained by age carries biological information. We assembled 2,846 photographs of 1,292 mice (four strains, 1 to 34 months old) from seven facilities and predicted age with a frozen self-supervised vision model (DINOv2) and a ridge regression, always tested on facilities the model had never seen. Absolute age transferred poorly between facilities (median absolute error 138 days), because each facility's photographs carried an offset. Relative age transferred well: among mice photographed in the same session, the older mouse was predicted older in 65% of pairs, rising above 95% for age differences over 500 days, and the later photograph of the same mouse was predicted older in 63% of repeat pairs. Sex, in comparison, was inferred more reliably (87%). Mice predicted older than their age were frailer (+0.12 SD per 100 days) and had shorter survival (hazard ratio 1.14 per 100 days), and fourth generation (G4) telomerase-deficient mice looked 151 days older than their wild-type controls. Routine photographs therefore carry a real biological age signal that can be read at no extra cost, best used to compare mice photographed together.

systems biology↗

Membrane estrogen receptor (GPER) and follicle-stimulating hormone receptor heteromeric complexes promote human ovarian follicle survival

Classically, follicle stimulating hormone receptor (FSHR) driven cAMP-mediated signaling boosts human ovarian follicle growth and would be essential for oocyte maturation. However, contradicting in vitro suggest a different view on physiological and clinical significance of FSHR-mediated cAMP signaling. We found that the G protein coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are effectively delivered upon equal expression levels of both receptors, while they are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with FSH responsiveness of patients undergoing controlled ovarian stimulation. Consistent with high FSHR expression levels during follicular selection, cell viability is dramatically reduced in FSHR overexpressing cells due to preferential coupling to the Gs protein/cAMP pathway. In contrast, FSHR/GPER heteromer formation resulted in FSH-triggered anti-apoptotic/proliferative signaling delivered via the G{beta}{gamma} dimer while heteromer impairment or GPER-associated Gs inhibitory protein complexes resulted in cell death. GPER-depleted granulosa cells have an amplified FSH-dependent decrease in cell viability and steroidogenesis, consistent with the requirement of estrogen signaling for successful oocyte growth. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation. One Sentence SummaryFSHR/GPER heteromers block cAMP-dependent selection of ovarian follicles and target tumor growth and poor FSH-response in women.

physiology↗