Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer's disease.

Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer's disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.

Skin Cancer Risk Is Increased by Somatic Mutations Detected Noninvasively in Healthy-Appearing Sun-Exposed Skin.

Skin cancer risk is increased by exposure to ultraviolet radiation (UVR). Because UVR exposure accumulates over time and lighter skin is more susceptible to UVR, age and skin tone are risk factors for skin cancer. However, measurements of somatic mutations in healthy-appearing skin have not been used to calculate skin cancer risk. In this study, we developed a noninvasive test that quantifies somatic mutations in healthy-appearing sun-exposed skin and applied it to a 1038-subject cohort. Somatic mutations were combined with other known skin cancer risk factors to train a model to calculate risk. The final model (DNA-Skin Cancer Assessment of Risk) was trained to predict personal history of skin cancer from age, family history, skin tone, and mutation count. The addition of mutation count significantly improved model performance (OR = 1.3, 95% confidence interval = 1.14-1.48; P = 5.3 × 10-6) and made a more significant contribution than skin tone. Calculations of skin cancer risk matched the known United States population prevalence, indicating that DNA-Skin Cancer Assessment of Risk was well-calibrated. In conclusion, somatic mutations in healthy-appearing sun-exposed skin increase skin cancer risk, and mutations capture risk information that is not accounted for by other risk factors. Clinical utility is supported by the noninvasive nature of skin sample collection through adhesive patches.

Pregnancy outcomes post-kidney transplantation across 23 years.

BACKGROUND: Pregnancy in kidney transplant recipients has become increasingly common. However, pregnancy carries higher risks to these patients compared to the general population. AIMS: To describe pregnancy outcomes in kidney transplant recipients. MATERIALS AND METHODS: We conducted a single-centre retrospective cohort study of kidney transplant recipients who delivered after 20 weeks gestation at a quaternary hospital in Victoria, Australia, between 2000 and 2022 inclusive. RESULTS: The study included 37 pregnancies from 27 patients, accounting for 38 infants. Over half of recorded pregnancies occurred in the past five years (56.8%, n = 21). There were high rates of pre-existing hypertension (75.7%, n = 28). Pregnancy-induced hypertension and pre-eclampsia were common antenatal complications (21.6%, n = 8 and 48.6%, n = 18 respectively). Soluble fms-like tyrosine kinase-1 / placental growth factor ratios were elevated in all patients who developed severe pre-eclampsia (16.2%, n = 6). The median gestational age at birth was 36.4 weeks (range 20-40.4, Q1 32.9, Q3 37.6) and 59.5% (n = 22) of births were preterm. Unplanned caesarean without labour was the most common mode of birth (35.1%, n = 13). The overall caesarean rate was 62.1% (n = 23). Post-partum haemorrhage complicated over half of pregnancies (56.8%, n = 21). Fifty percent (n = 19) of infants were admitted for neonatal care, in particular neonatal intensive care, and had low birthweights under 2500 g. While there was a transient deterioration in kidney function, there was no graft rejection within one year of birth. CONCLUSIONS: Clinicians should consider the high rates of pre-existing hypertension, preterm birth, and caesarean birth when counselling and managing pregnant kidney transplant recipients.