Summary Prolonged fasting (PF) promotes stress resistance but its effects on longevity are poorly understood. We show that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes. In mice, four days of a diet that mimics fasting (FMD), developed to minimize the burden of PF, decreased the size of multiple organs/systems; an effect followed upon re-feeding by an elevated number of progenitor and stem cells and regeneration. Bi-monthly FMD cycles started at middle age extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions, rejuvenated the immune system, and retarded bone mineral density loss. In old mice, FMD cycles promoted hippocampal neurogenesis, lowered IGF-1 levels and PKA activity, elevated NeuroD1, and improved cognitive performance. In a pilot clinical trial, three FMD cycles decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan.

Summary Dietary interventions have not been effective in the treatment of multiple sclerosis (MS). Here we show that periodic 3 day cycles of a fasting mimicking diet (FMD) are effective in ameliorating demyelination and symptoms in a murine experimental autoimmune encephalomyelitis (EAE) model. The FMD reduced clinical severity in all mice, and completely reversed symptoms in 20% of the animals. These improvements were associated with increased corticosterone levels and Treg cell number, reduced levels of pro-inflammatory cytokines, TH1 and TH17 cells, and antigen presenting cells (APCs). Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in response to both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that a FMD or a chronic ketogenic diet are safe, feasible and potentially effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients (NCT01538355).

Objectives Outcomes beyond 10 years for David V valve-sparing aortic root replacement (VSARR) in bicuspid aortic valve (BAV) patients have yet to be explored. We investigated long-term outcomes after BAV VSARR compared to VSARR for tricuspid aortic valve (TAV) patients. Methods A total of 677 patients with BAV (n = 171) and TAV (n = 506) underwent VSARR between 2005-2020 from two aortic centers, excluding those with dissection, endocarditis, stenosis, or prior aortic valve surgery. Multivariable Cox regression compared adjusted survival over a 12-year period. Fine and Gray competing risk regression compared risk and cumulative incidence of reoperation/reintervention. Propensity score matching (PSM) created balanced groups, and landmark analysis isolated outcomes beginning four years postoperatively. Finally, longitudinal mixed modeling assessed aortic valve deterioration on echocardiogram. Results No difference was observed in 12-year survival of BAV vs TAV (PSM 92.0% vs 89.9%, p = 0.97; multivariable HR 0.76, 95% CI 0.34-1.69. p = 0.51). Adjusted 12-year cumulative incidence and risk of aortic valve and/or proximal aorta reoperation/reintervention were not observed to be different (15.7% BAV vs 5.7% TAV, p = 0.37; sHR 1.54, 95% CI 0.60-3.94, p = 0.36); however, landmark analysis showed increased incidence of late reoperation/reintervention in BAV vs TAV (11.7% vs 0.0%, p = 0.04). BAV was not associated with aortic valve deterioration over time (BAV coefficient ± standard error: 0 ± 0.30, p = 1). Conclusions VSARR for bicuspid aortic valve patients has excellent 12-year survival and low reoperation/reintervention rates, that were not observed to be different from TAV patients. However, higher incidence of reoperation/reintervention was observed in the late years after BAV VSARR. Our study provides key information for surgical consultation of patients with bicuspid aortopathy.