Exploring the Relationship Between Insulin Resistance, Liver Health, and Restrictive Lung Diseases in Type 2 Diabetes.

: Restrictive lung disease (RLD) is a potential complication in type 2 diabetes (T2D), but its relationship with insulin resistance and liver-related metabolic dysfunction remains unclear. This study evaluated the association between lung function and metabolic markers in T2D and retrospectively assessed whether metabolic improvements from dietary intervention were accompanied by changes in lung function. : This cross-sectional analysis included 184 individuals (101 with T2D, 33 with prediabetes, and 50 glucose-tolerant individuals).

Dietary Amino Acids and Risk of Stroke Subtypes: Results from 3 Large Prospective Cohort Studies.

Background: Differences in dietary protein have been associated with stroke risk, with possible heterogeneity in associations by stroke type or food sources of protein.

Objectives: We examined the associations of individual dietary amino acids, as the constituents of dietary protein, with risks of ischemic, hemorrhagic, and total stroke.

Methods: We analyzed data from 73,830 females in the Nurses' Health Study (1984-2012), 92,333 females in the Nurses' Health Study II (1991-2013), and 43,268 males in the Health Professionals Follow-Up Study (1986-2016).

The time is now: accounting for time-of-day effects to improve reproducibility and translation of metabolism research.

The constant expansion of the field of metabolic research has led to more nuanced and sophisticated understanding of the complex mechanisms that underlie metabolic functions and diseases. Collaborations with scientists of various fields such as neuroscience, immunology and drug discovery have further enhanced the ability to probe the role of metabolism in physiological processes. However, many behaviours, endocrine and biochemical processes, and the expression of genes, proteins and metabolites have daily ~24-h biological rhythms and thus peak only at specific times of the day.

Chemosensory and cardiometabolic improvements after a fasting-mimicking diet: A randomized cross-over clinical trial.

Obesity is associated with a decrease in chemosensory perception acuity and increased disease risk, pointing to the need for feasible interventions that affect smell, taste, and cardiometabolic markers. Here, subjects with overweight/obesity are treated with six monthly cycles of a fasting-mimicking diet (FMD) lasting 5 days followed by a normal diet for the rest of the month to determine their effects on chemosensory function and cardiometabolic risk factors. Both arms of the 102 randomized cross-over trial participants indicate FMD-dependent improvements in a wide range of taste and smell chemosensory functions.

Fasting-mimicking diet potentiates anti-tumor effects of CDK4/6 inhibitors against breast cancer by suppressing NRAS- and IGF1-mediated mTORC1 signaling.

Fasting-mimicking diet (FMD) cycles, defined as 3-5 day periods of a calorie-restricted, low-protein, low-carbohydrate, and high-fat diet, have emerged as a dietary approach to delay cancer initiation and progression in both autograft and xenograft mouse models and as a safe and feasible approach to decrease risk factors for cancer and other age-related pathologies in humans. A substantial number of pre-clinical studies focused on various tumor types have shown that fasting/FMDs can potentiate the efficacy of various standard-of-care cancer therapies but also modulate the immune system to promote a T cell-dependent attack of tumor cells. Importantly, combining drug treatment with fasting/FMDs can overcome acquired drug resistance which frequently emerges and reduces long-term treatment benefits.

Nutrition, GH/IGF-1 signaling, and cancer.

Cancer is the second leading cause of death in the United States and among the most prevalent diseases globally, with an incidence expected to grow because of smoking, pollution, poor dietary habits, obesity, and the rise in the older population. Given their ability to reduce risk factors, albeit with varying efficacy, nutrition and fasting could help prevent cancer and other age-related disorders. Calorie restriction (CR), various forms of intermittent fasting (IF) or periodic fasting (PF), and fasting-mimicking diets (FMDs) have been shown to improve health span, increase lifespan, and prevent or postpone cancer in rodents.

Cyclic fasting-mimicking diet in cancer treatment: Preclinical and clinical evidence.

In preclinical tumor models, cyclic fasting and fasting-mimicking diets (FMDs) produce antitumor effects that become synergistic when combined with a wide range of standard anticancer treatments while protecting normal tissues from treatment-induced adverse events. More recently, results of phase 1/2 clinical trials showed that cyclic FMD is safe, feasible, and associated with positive metabolic and immunomodulatory effects in patients with different tumor types, thus paving the way for larger clinical trials to investigate FMD anticancer activity in different clinical contexts. Here, we review the tumor-cell-autonomous and immune-system-mediated mechanisms of fasting/FMD antitumor effects, and we critically discuss new metabolic interventions that could synergize with nutrient starvation to boost its anticancer activity and prevent or reverse tumor resistance while minimizing toxicity to patients.

Normal or improved cardiovascular risk factors in IGF-I-deficient adults with growth hormone receptor deficiency.

Background: Human subjects with generalized growth hormone (GH) insensitivity due to GH receptor deficiency (GHRD)/Laron syndrome display a very low incidence of insulin resistance, diabetes, and cancer, as well as delayed age-related cognitive decline. However, the risk of cardiovascular disease (CVD) in these subjects is poorly understood. Here, we have assessed cardiovascular function, damage, and risk factors in GHRD subjects and their relatives.

Exploring juventology: unlocking the secrets of youthspan and longevity programs.

In recent decades, the study of biological aging has evolved from simplistic theories like the free radical theory to more complex and nuanced perspectives. In particular, the identification of evolutionary conserved genes and signaling pathways that can modulate both lifespan but also healthspan has resulted in the expanding understanding of the link between nutrients, signal transduction proteins, and aging along with substantial support for the existence of multiple "longevity programs," which are activated based on the availability of nutrients. Periodic fasting and other dietary restrictions can promote entry into a longevity program characterized by cellular protection and optimized function, and the activation of regenerative processes that lead to rejuvenation.

Integration of a fasting-mimicking diet programme in primary care for type 2 diabetes reduces the need for medication and improves glycaemic control: a 12-month randomised controlled trial.

Aims/hypothesis: The aim of this study was to evaluate the impact on metabolic control of periodic use of a 5-day fasting-mimicking diet (FMD) programme as an adjunct to usual care in people with type 2 diabetes under regular primary care surveillance.

Methods: In this randomised, controlled, assessor-blinded trial, people with type 2 diabetes using metformin as the only glucose-lowering drug and/or diet for glycaemic control were randomised to receive 5-day cycles of an FMD monthly as an adjunct to regular care by their general practitioner or to receive regular care only. The primary outcomes were changes in glucose-lowering medication (as reflected by the medication effect score) and HbA levels after 12 months.

Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk.

In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging) and increased lymphoid to myeloid ratio: an indicator of immune system age. Based on a validated measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.

Cyclic Fasting-Mimicking Diet Plus Bortezomib and Rituximab Is an Effective Treatment for Chronic Lymphocytic Leukemia.

Unlabelled: Cyclic fasting-mimicking diet (FMD) is an experimental nutritional intervention with potent antitumor activity in preclinical models of solid malignancies. FMD cycles are also safe and active metabolically and immunologically in cancer patients. Here, we reported on the outcome of FMD cycles in two patients with chronic lymphocytic leukemia (CLL) and investigated the effects of fasting and FMD cycles in preclinical CLL models.

Ketone bodies in cell physiology and cancer.

Ketogenic diets (KDs), fasting, or prolonged physical activity elevate serum ketone bodies (KBs) levels, providing an alternative fuel source for the brain and other organs. However, KBs play pleiotropic roles that go beyond their role in energy production. KBs can act as signaling metabolites, influence gene expression, proteins' posttranslational modifications (PTMs), inflammation, and oxidative stress.

Nutrition and dietary restrictions in cancer prevention.

The composition and pattern of dietary intake have emerged as key factors influencing aging, regeneration, and consequently, healthspan and lifespan. Cancer is one of the major diseases more tightly linked with aging, and age-related mortality. Although the role of nutrition in cancer incidence is generally well established, we are far from a consensus on how diet influences tumour development in different tissues.

Fasting-Mimicking Diet Inhibits Autophagy and Synergizes with Chemotherapy to Promote T-Cell-Dependent Leukemia-Free Survival.

Fasting mimicking diets (FMDs) are effective in the treatment of many solid tumors in mouse models, but their effect on hematologic malignancies is poorly understood, particularly in combination with standard therapies. Here we show that cycles of a 3-day FMD given to high-fat-diet-fed mice once a week increased the efficacy of vincristine to improve survival from BCR-ABL B acute lymphoblastic leukemia (ALL). In mice fed a standard diet, FMD cycles in combination with vincristine promoted cancer-free survival.

Fasting mimicking diet cycles versus a Mediterranean diet and cardiometabolic risk in overweight and obese hypertensive subjects: a randomized clinical trial.

Abnormalities in the vascular endothelium such as impaired vasodilation can contribute to atherosclerosis and hypertension. Here we have performed a single-center randomized clinical trial to evaluate the efficacy of 4 months of a continuous Mediterranean diet (MD) regimen as compared to 4 cycles of fasting mimicking diet (FMD) administered for only 5 days/month on endothelial function, measured as reactive hyperemia index (RHI) and large/small-resistance artery compliance (AC1/AC2), and on other cardiometabolic risk factors, in hypertensive patients with obesity/excess weight [both sexes, body mass index (BMI) ≥ 28, RHI ≤ 2.0, and/or small-resistance artery compliance (AC2) ≤ 5.

Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients.

Background And Aim: Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D).

Study Design And Methods: Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.

Fasting and fasting mimicking diets in cancer prevention and therapy.

Fasting mimicking diets (FMDs) are emerging as effective dietary interventions with the potential to improve healthspan and decrease the incidence of cancer and other age-related diseases. Unlike chronic dietary restrictions or water-only fasting, FMDs represent safer and less challenging options for cancer patients. FMD cycles increase protection in healthy cells while sensitizing cancer cells to various therapies, partly by generating complex environments that promote differential stress resistance (DSR) and differential stress sensitization (DSS), respectively.

Biology of Stress Responses in Aging.

On April 28, 2022, a group of scientific leaders gathered virtually to discuss molecular and cellular mechanisms of responses to stress. Conditions of acute, high-intensity stress are well documented to induce a series of adaptive responses that aim to promote survival until the stress has dissipated and then guide recovery. However, high-intensity or persistent stress that goes beyond the cell's compensatory capacity are countered with resilience strategies that are not completely understood.

Fasting and cancer: from yeast to mammals.

Fasting and fasting mimicking diets extend lifespan and healthspan in mouse models and decrease risk factors for cancer and other age-related pathologies in humans. Normal cells respond to fasting and the consequent decrease in nutrients by down-regulating proto-oncogene pathways to enter a stress-resistant mode, which protects them from different cancer therapies. In contrast, oncogene mutations and the constitutive activation of pathways including RAS, AKT, and PKA allow cancer cells to disobey fasting-dependent anti-growth signal.

Breakfast keeps hunger in check.

Many studies associate skipping breakfast with increased overall and disease-specific mortality. In this issue, studies by Ruddick-Collins et al. and Vujović et al.