The Role Of Nutrient Sensing Pathways In Delaying Ageing

Caloric restriction (CR) without malnutrition is a robust dietary intervention that extends lifespan and improves health in virtually every species studied. Recently, some of the mechanisms for the effects of CR on ageing have been elucidated, including several cellular master switches collectively called “nutrient sensing pathways”. CR is not sustainable in humans, therefore research has begun to focus on developing ad libitum-fed diets that maximise lifespan and healthspan. This thesis presents research on the effects of diets with differing ratios of macronutrients on nutrient sensing pathways, and their impact on ageing and age-related end points. This is achieved using the paradigm of the Geometric Framework (GF), an analytical tool used to disentangle the effects of various nutritional components such as macronutrient ratios and energy intakes on outcomes. Using the GF, a large-scale nutritional study is used to examine the aging process through genotypic and phenotypic changes in nutrient sensing pathways, and their relationship with parameters of health and lifespan. Taken together, the results presented here form a case that manipulation of the nutrient sensing pathways are a mechanism for the beneficial effects of dietary interventions on ageing and health. Further investigation of these growth pathways could help to develop guidelines for optimal nutritional intake, or form the basis for pharmacological interventions targeted at prolonging lifespan, healthspan, and promoting health in old age, without the use of long-term dietary manipulation. The algorithmic tools developed here, also have the potential to be applied to a wider array of experimental fields, supporting the overarching experimental model of comparing multi-dimensional inputs on responses, as opposed to the more commonly used control versus treatment model that is largely seen in scientific research

Dietary Protein to Carbohydrate Ratio and Caloric Restriction: Comparing Metabolic Outcomes in Mice

Both caloric restriction (CR) and low-protein, high-carbohydrate (LPHC) ad-libitum-fed diets increase lifespan and improve metabolic parameters such as insulin, glucose, and blood lipids. Severe CR, however, is unsustainable for most people; therefore, it is important to determine whether manipulating macronutrient ratios in ad-libitum-fed conditions can generate similar health outcomes. We present the results of a short-term (8 week) dietary manipulation on metabolic outcomes in mice. We compared three diets varying in protein to carbohydrate ratio under both CR and ad libitum conditions. Ad libitum LPHC diets delivered similar benefits to CR in terms of levels of insulin, glucose, lipids, and HOMA, despite increased energy intake. CR on LPHC diets did not provide additional benefits relative to ad libitum LPHC. We show that LPHC diets under ad-libitum-fed conditions generate the metabolic benefits of CR without a 40% reduction in total caloric intake

Defining the nutritional and metabolic context of FGF21 using the geometric framework

Fibroblast growth factor 21 (FGF21) is the first known endocrine signal activated by protein restriction. Although FGF21 is robustly elevated in low-protein environments, increased FGF21 is also seen in various other contexts such as fasting, overfeeding, ketogenic diets, and high-carbohydrate diets, leaving its nutritional context and physiological role unresolved and controversial. Here, we use the Geometric Framework, a nutritional modeling platform, to help reconcile these apparently conflicting findings in mice confined to one of 25 diets that varied in protein, carbohydrate, and fat content. We show that FGF21 was elevated under low protein intakes and maximally when low protein was coupled with high carbohydrate intakes. Our results explain how elevation of FGF21 occurs both under starvation and hyperphagia, and show that the metabolic outcomes associated with elevated FGF21 depend on the nutritional context, differing according to whether the animal is in a state of under- or overfeeding.11 page(s

Abstracts of National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020

This book presents the abstracts of the papers presented to the Online National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020 (RDMPMC-2020) held on 26th and 27th August 2020 organized by the Department of Metallurgical and Materials Science in Association with the Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, India. Conference Title: National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020Conference Acronym: RDMPMC-2020Conference Date: 26–27 August 2020Conference Location: Online (Virtual Mode)Conference Organizer: Department of Metallurgical and Materials Engineering, National Institute of Technology JamshedpurCo-organizer: Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, IndiaConference Sponsor: TEQIP-