Rapamycin extends life and health in C57BL/6 mice.

Target of rapamycin inhibition by rapamycin feeding has previously been shown to extend life in genetically heterogeneous mice. To examine whether it similarly affected mouse health, we fed encapsulated rapamycin or a control diet to C57BL/6Nia mice of both sexes starting at 19 months of age. We performed a range of health assessments 6 and 12 months later. Rapamycin feeding significantly reduced mTOR activity in most but not all tissues. It also reduced total and resting metabolic rate during the light (inactive) phase of the light:dark cycle in females only but had no effect on spontaneous activity or metabolism during the dark (active) phase of either sex. Males only had less fragmented sleep when fed rapamycin, whereas stride length and rotarod performance were improved in both sexes. Survival was also improved by this late-life rapamycin feeding, and some pathological lesions were delayed. We found no adverse health consequences associated with rapamycin treatment.

Progression of diabetic maculopathy in patients on the Wellington Diabetic Screening Programme initially graded M3.

AIM: To determine the likelihood of progression from M3 grade maculopathy, and therefore the safety of these patients remaining under the care of a primary screener. METHODS: Patients graded M3 at diabetic screening were selected from the Wellington screening database. Photographs for this visit and the subsequent visit were obtained, and graded by a consultant ophthalmologist. Photographs graded M3 were included and progression of maculopathy between visits, number of patients with a reduction in vision and duration between visits were determined. RESULTS: Mean duration between visits for all patients was 255 (plus or minus 59.5) days. Of the 54 eyes studied, 15 or 33.3% progressed to M4 maculopathy at the subsequent visit. Despite progressing from M3 to M4, none had a reduction of vision by more than one line of Snellen acuity at follow up due to diabetic maculopathy. CONCLUSIONS: Rates of progression of maculopathy from M3 to M4 were of clinical significance. Despite this none had worsening visual acuity due to diabetic eye disease. This suggests patients with M3 maculopathy could be maintained under a primary screening programme, as is the case in the United Kingdom.

Dietary restriction but not rapamycin extends disease onset and survival of the H46R/H48Q mouse model of ALS.

Dietary restriction (DR) and rapamycin (Rapa) have been shown to increase the lifespan of a variety of organisms leading to the speculation that these interventions increase lifespan through related mechanisms. However, both these interventions have a detrimental effect in the G93A mutant mouse model of amyotrophic lateral sclerosis (ALS). Our previous work indicated that different ALS SOD1 mutant mouse models differ in disease pathogenesis; therefore in this study we measured the effect of DR and Rapa in a second ALS mutant mouse model (the H46R/H48Q mutant). Interestingly, in mice expressing this mutant SOD1 protein, DR significantly delays disease onset and extends lifespan, while Rapa has no effect. These findings suggest that: (1) the effect of DR in ALS is not mediated through pathways common with Rapa, (2) the deleterious effect of DR and Rapa in the G93A ALS mouse model may not be universal to disease caused by all SOD1 mutations, and (3) the results reinforce our previous conclusions that the pathogenic mechanisms in G93A and H46R/H48Q mice are distinct.