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Background Caloric restriction (CR) without micronutrient deficiency has been shown to increase both lifespan and healthspan. In animals, CR has been demonstrated to increase glutathione (GSH), a neuroprotective antioxidant, in the brain and preserve brain mitochondrial function by altering neuroenergetics. In humans it has been associated with improvements in mood states and cognitive function. However, most CR studies have employed a 30–60% reduction in calories which is likely too stringent for most people to adhere to long-term. Thus, there is an unmet need for nutritional supplements which can mimic the biological effects of CR, without the need for calorie limitations. Aim The purpose of the present randomized, placebo-controlled clinical trial was to use Proton (1H) Magnetic Resonance Spectroscopic (MRS) measurements to determine non-invasively whether a blend of micronutrients, a putative CR mimetic, positively modulates metabolites related to neuroprotection and neuroenergetics in the brain. Methods Healthy middle-aged men and women (N = 63 [33 women]; age: 40–60 years) were randomized in a double-blind manner to 6 weeks supplementation with either the putative CR mimetic or placebo. At baseline and 6 weeks, subjects underwent MRS at 3 T to investigate changes in brain chemistry, including the neurometabolites: GSH, Glutamate (Glu), Glutamine (Gln) and N-Acetylaspartate (NAA). Results GSH, a marker of antioxidant and cellular redox status, increased in the brain of participants in the supplement group. The supplement group also showed an increase in the Glu/Gln ratio, a marker of excitatory neurotransmission and bioenergetics. A trend for an increase in NAA/H2O, a marker of neuronal integrity, was observed in females in the supplement group. Conclusions The present study reveals that 6-weeks daily supplementation with a micronutrient blend elicits positive changes in brain neurochemistry. This is the first study to demonstrate that a putative CR mimetic increases brain GSH concentrations and improves neuroprotection and neuroenergetics in the brain of healthy humans. This study was registered at www.clinicaltrials.gov as NCT02439983.

OBJECTIVES: Consumption of supplements have been found to improve skin health, but there is only a limited number of studies to support these claims. The main objective of this single center, randomized placebo-controlled study was to determine the effects of a nutritional supplement containing collagen peptides, wheat extract oil containing ceramides, and lutein on skin appearance in healthy adults. METHODS: Sixty healthy, nonsmoking men and women between the ages of 40 and 75 years with Fitzpatrick skin types I and II were recruited to participate in the study. The variables measured were changes in skin attributes including skin color, skin carotenoids levels, skin hydration, and visible results as assessed by a dermatologist and self-assessment between groups given supplement: collagen peptides, ceramides, and lutein (CCL) or placebo. The study also investigated if using a facial cleansing device along with CCL influenced facial skin appearance. RESULTS: Skin carotenoid levels significantly increased from baseline with CCL at 30 and 120d with a mean increase of 10,750 Raman Intensity Units (RIUs) following 120d supplementation. Significant improvements in facial skin radiance, texture, and overall appearance were found for CCL, cleansing device or combination of both. An increase was found in skin facial color (b(*)) at 30 and 120d with CCL supplementation while placebo treatment was unchanged between baseline and 30d, but then increased between 30 and 120d. No changes in lines and skin firmness were noted. CONCLUSIONS: Supplementation for 120d with CCL with and without a cleansing device supported skin health and improved several skin attributes thus confirming evidence of benefit on skin health and identifying potential for added benefit of device along with supplementation. FUNDING SOURCES: NSE Products, Inc., Provo, Utah.

Bronchial-associated immune development is critically important to protect neonates from respiratory infections. Herein, bronchial-associated immune development in formula-fed and sow-reared pigs is described. Colostrum-fed newborn piglets were fed medicated sow milk replacer formula beginning at 48 h of life or remained with the sow. Blood and tissues were sampled at one-week (d7) and three-weeks (d21) of age. Lymphocyte subpopulations, including T helper 2, cytotoxic T, memory T, and NK cells, in peripheral blood, mediastinal lymph nodes, and thoracic lymph nodes were identified using flow cytometry. Additionally, IL-1β, IL-6, IL-12, TNFα, TGF-β1, TGF-β2, IFNα, IFNβ, and dectin gene expression were analyzed by quantitative RT-PCR. Total IgG, IgM, and IgA concentrations in serum were analyzed. Dietary and developmental effects were observed. This set of baseline measurements provides a framework for future respiratory challenge studies where the effects of diet on the neonate's ability to resist and/or recover from infection can be tested.

Identification of caloric restriction mimetics (CRMs), compounds that mimic the beneficial effects of caloric restriction (CR) without limiting energy intake would be a scientific advancement. This study investigated transcriptomics elicited by a putative CRM nutrient blend compared to CR in diverse tissues following long-term feeding in 4 groups of B6C3F1 mice: Young Controls (YC; 5 months) and 3 groups treated from 14–30 months: Old Controls (OC), Old CR (OCR; 25% CR) and Old Supplemented (OS). Gene expression profiling in cerebral cortex (CC), skeletal muscle (SKL), heart (HRT), white adipose (WAT)and liver (LVR) was performed with Affymetrix Mouse 2.0ST arrays. This was followed by a dose-response study in C. elegans investigating longevity and mobility. Principal component analysis revealed that gene expression profiles of YC and OC were distinct from one another in all tissues except WAT at 30 months. The OS mimicked OCR transcriptomics most dramatically in tissues most relevant to aging and age-associated diseases, CCT, HRT and SKL. In C. elegans, the blend mimicked the known benefits of CR, increasing lifespan and vitality in a dose-dependent manner. These CRM effects may have positive implications for healthy human aging or ‘youthspan’ and warrant further investigation.

Identification of caloric restriction mimetics (CRMs), compounds that mimic the beneficial effects of caloric restriction (CR) without restriction of dietary energy would be an advancement in anti-aging science. The present study investigated whether the transcriptional profiles of a putative CRM nutrient blend could mimic that of CR in diverse tissues following long-term feeding in B6C3F1 male mice. Study design: Young Controls (YC; 5 mo.) and 3 groups treated from 14-30 mo.: Old Controls (OC), Old CR (OCR; 25% CR) and Old Supplemented (OS); n=7/group. Gene expression profiling in cerebral cortex (CCT), skeletal muscle (gastrocnemius)(SKL), heart (HRT), white adipose tissue (WAT) and liver (LVR) was performed using Affymetrix Mouse 2.0ST arrays. Principal component analysis revealed that gene expression profiles of YC and OC were distinct from one another in all tissues at 30 months. Using differential analysis, genes commonly expressed in OCR and OS groups compared to the OC group were identified in CCT (3,468), SKL (2,386), HRT (3,523), LVR (1,276) and WAT (683). The OS group mimicked OCR transcriptional profiles most dramatically in CCT, HRT and SKL, tissues highly relevant to aging and age-associated diseases. These CRM effects, elicited by a mid-life intervention, may have positive implications for healthy human aging or ‘youthspan’ and warrant further investigation.

An increased permeability of the intestinal barrier is proposed as one underlying factor of obesity-associated pathologies. Consumption of high fat diet (HFD) is associated with intestinal permeabilization and increased paracellular transport of endotoxins, which can promote steatosis and insulin resistance. We investigated the capacity of dietary anthocyanidins (AC) to mitigate steatosis and improve insulin sensitivity in HFD-fed mice. Male C57BL/6 J mice were fed for 14 w control (C) or high fat (HF) diet, with or without supplementation with 2, 20, or 40 mg/kg BW of a blend of AC-rich plant extracts (ACE). The consumption of HFD caused overweight and insulin resistance, which were mitigated by ACE consumption. Concurrently, ACE prevented HFD-induced intestinal permeabilization, altered expression of ileum tight junction proteins (decreased ZO-1 and occludin) and endotoxemia. AC protection of barrier permeability is in part due to the inhibition of HFD-induced ileum ERK1/2 and AMPK activation, increased GLP-2 levels, and mitigation of dysbiosis. Consistently, the highest AC dose prevented steatosis and improved blood and liver inflammation and oxidative stress. Findings suggest that ACE supplementation could be an important strategy to mitigate obesity and Western style diets-associated insulin resistance in part through the preservation of intestinal barrier integrity.