Here is a link to the full paper and Summary...
Prolonged fasting (PF) promotes stress resis- tance, 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, 4 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 regenera- tion. 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/bio- markers for aging, diabetes, cardiovascular dis- ease, and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan.
...and this section on adult
Adult neurogenesis plays an important role in learning and memory (Clelland et al., 2009; Deng et al., 2010; Mattson, 2012). To determine whether the diet affected neurogenesis, we measured BrdU incorporation in the subgranular layer of control mice at the age of 8 weeks, 12 weeks, 6 months, and 24 months (Figure 4B). Similarly to previously reported data, we observed an age-dependent decline in BrdU incorporation in the dentate gyrus (Lee et al., 2012c) (Figure 4B). To assess whether the cognitive improvements in the FMD group are asso- ciated with neural regeneration, we measured the proliferative index of DCX+ immature neurons in the sub-granular cell layer of the dentate gy- rus. BrdU+ or BrdU+ DCX+ double-label- ing indicated an increased proliferation of immature neurons in the FMD group compared to that in controls (Figures 4C–4E). To investigate mechanisms of FMD-induced neurogenesis, we fed 6-month-old mice, in which cellular prolif-
eration in the dentate gyrus is reduced by more than 50% compared to that in 8-week-old mice (Figure 4B), with a single cycle of the FMD. After 72 hr on the FMD, we observed a reduc- tion in circulating (Figure S1E) and hippocampal IGF-1 (Figure 4F) but increased IGF-1 receptor mRNA expression in the dentate gyrus region of the hippocampal formation (Figure 4G). Micro- dissected dentate gyrus-enriched samples from FMD mice displayed a major reduction in PKA activity (Figure 4H) and a 2-fold induction in the expression of NeuroD1 (Figure 4I), a tran- scription factor important for neuronal protection and differenti- ation (Gao et al., 2009). Similarly, a single cycle of the FMD increased radial glia-like cells (type I) and non-radial precursor (type II) neural stem cells (Figures S4B, S4C, S4F, and S4G), immature neurons (Figures S4D and S4I–S4Q), and the dendrite-covered area (Figures S4E and S4H) in CD-1 mice.
These results in two genetic backgrounds indicate that the FMD promotes neurogenesis in adult mice. Notably, the brain did not undergo a measurable weight reduction during the FMD, indicating that regeneration can also occur independently of the organ size increase after refeeding. Thus, we hypothesize that alterations in circulating factors, such as the reduction in IGF-1 levels and PKA signaling, can induce pro-regenerative changes that are both dependent and independent of the major cell proliferation that occurs during re-feeding, in agreement with our previous finding in bone marrow and blood cells (Cheng et al., 2014). Most likely, the increase in IGF-1 and PKA after re- feeding also contributes to the proliferative and regenerative process, raising the possibility that both low and high levels of these proteins can promote regeneration depending on the timing of their expression. Alternatively, the FMD may increase survival of newly differentiated neurons, as observed in the den- tate gyrus of alternate day-fed rodents (Lee et al., 2002; Mattson et al., 2001). The observed improvements in cognitive perfor- mance in the FMD cohort might be affected by a PKA/CREB- dependent regulation of NeuroD1 (Cho et al., 2012; Sharma et al., 1999), which is known to increase neuronal survival and differentiation of hippocampal progenitors (Roybon et al., 2009), enhance functional integration of new neurons, and alle- viate memory deficits in a mouse model of Alzheimer’s disease (Richetin et al., 2015).
Note that the fasting phase diet was pretty low protein, high fat, and moderate carbs....and also "plant-based"...
The develop- ment of the human diet took into account feasibility (e.g., high adherence to the dietary protocol) and therefore was designed to last 5 days every month and to provide between 34% and 54% of the normal caloric intake with a composition of at least 9%–10% proteins, 34%–47% carbohydrates, and 44%–56% fat.
The human fasting mimicking diet (FMD) program is a plant-based diet program designed to attain fasting-like effects while providing micronutrient nourishment (vitamins, minerals, etc.) and minimize the burden of fasting. It comprises proprietary vegetable-based soups, energy bars, energy drinks, chip snacks, chamomile flower tea, and a vegetable supplement formula tablet (Table S4). The human FMD diet consists of a 5 day regimen: day 1 of the diet supplies $1,090 kcal (10% protein, 56% fat, 34% carbohydrate), days 2–5 are identical in formulation and provide 725 kcal (9% protein, 44% fat, 47% carbohydrate).
Direct link to Supplementary Materials...http://www.cell.com/cms/attachment/2033218219/2049335774/mmc1.pdf