NUTRIGERONTOLOGY

​NUTRIGERONTOLOGY: A NEW SCIENTIFIC DISCIPLINE

Nutrigerontology is a new scientific field that is a synthesis of medicine, biogerontology (the science of aging) and nutrition.

Dr. Kris Verburgh introduced the concept of nutrigerontology in the international scientific journal ‘Aging Cell’.

Nutrigerontology studies how substances, foods and diets can slow down or speed up the aging process and influence the risk of aging-related diseases like cardiovascular disease, diabetes or dementia.

You can download the scientific paper of Dr. Verburgh about nutrigerontology here:

speaker
Nutrigerontology wants to bridge the gap between biogerontology and medicine, with the aim to prevent, reduce the risk, treat and even reverse various aging-associated diseases that afflict our society, like cardiovascular disease, Alzheimer’s disease and type 2 diabetes.

If we better understand the mechanisms of the aging process, we can develop more effective diet, nutrition and treatment guidelines that can substantially reduce the risk and burden of highly prevalent aging-associated diseases.

In view of the current epidemic of aging-related and metabolic diseases, there is an urgent need for a more interdisciplinary approach to address these issues.

NUTRIGERONTOLOGY: WHY WE NEED A NEW SCIENTIFIC DISCIPLINE TO DEVELOP DIETS AND GUIDELINES TO REDUCE THE RISK OF AGING-RELATED DISEASES

Author: Kris Verburgh, MD (Free University of Brussels)
Published in: Aging Cell

SUMMARY

Many diets and nutritional advice are circulating, often based on short- or medium-term clinical trials and primary outcomes, like changes in LDL cholesterol or weight. It remains difficult to assess which dietary interventions can be effective in the long term to reduce the risk of aging-related disease and increase the (healthy) lifespan. At the same time, the scientific discipline that studies the aging process has identified some important nutrient-sensing pathways that modulate the aging process, such as the mTOR and the insulin/insulin-like growth factor signaling pathway. A thorough understanding of the aging process can help assessing the efficacy of dietary interventions aimed at reducing the risk of aging-related diseases. To come to these insights, a synthesis of biogerontological, nutritional, and medical knowledge is needed, which can be framed in a new discipline called ‘nutrigerontology’.

INTRODUCTION

Great progress has been made in the course of recent decades in the field of aging research. Biogerontology, the science that studies aging, uncovered some important molecular pathways that are major modulators of the aging process (Kenyon, 2010; Fontana et al., 2010; Bartke et al., 2013). At the same time, society is confronted with an ever-increasing rise in the prevalence of aging-related diseases, such as cardiovascular disease, type 2 diabetes, and Alzheimer’s disease. Extending knowledge from biogerontology to clinical medicine and nutritional science can help discover adequate dietary recommendations to prevent or slow down the progress of various aging-related diseases. This knowledge can be framed into ‘nutrigerontology’, a new scientific discipline that encompasses biogerontology, medicine, and dietetics. Nutrigerontology researches how food substances, foods, food patterns, and diets influence the risk of aging-related diseases and (healthy) lifespan. Nutrigerontology can also be considered as a practical application of biogerontology. This article wants to clarify how biogerontological insights can be used to create dietary recommendations that can reduce the risk of various aging-related diseases that are on the rise in both developed and developing countries.

​REDUCED INSULIN/IGF-1 AND MTOR SIGNALING INCREASES LIFESPAN

  • In the field of biogerontology, the two most well-known pathways implicated in the aging process are the insulin/insulin-like growth factor signaling pathway (IIS pathway) (Bartke et al., 2013) and the mammalian or mechanistic target of rapamycin (mTOR) pathway (Johnsonet al., 2013).
  • We will initially focus on these two canonical pathways to show how a better understanding of the aging process can help to develop better long-term diet recommendations.
  • The mTOR and IIS pathways are nutrient-sensing pathways, implying that they are activated by nutrients that we eat, such as carbohydrates (which mainly activate the IIS pathway, but also the mTOR pathway) (Bartke et al., 2013) and amino acids (which mainly activate the mTOR pathway, but also the IIS pathway) (Wullschleger et al., 2006).
  • The IIS pathway exerts its effects through transmembrane insulin and IGF-1 receptors, which initiate glucose uptake in the cell, and stimulate cell growth and cell proliferation.
  • The mTOR protein is intracellularly located and a potent stimulator of protein translation.
  • A mounting body of research shows that loss of function of the IIS pathway and mTOR pathway increases lifespan. Modulating these pathways, genetically or nutritionally, can impact the rate of aging and postpones the advent of aging-related diseases.
  • For example, mice with a fat-specific insulin receptor knockout (FIRKO) genotype live 18% longer (Blüher et al., 2003) and reducing insulin receptor signaling in the mouse brain extended lifespan up to 18% (Taguchi et al., 2007).
  • Homozygous deletion of the insulin receptor substrate 1 (Irs1-/-), an effector of the insulin receptor, increased median lifespan by 32% in female mice.
  • However, deletion of IRS-1 in male mice did not lead to an increased lifespan (Selman et al., 2008). Mice heterozygous for the IGF-1 receptor (Igf1r+/-) live on average 26% longer than their wild-type littermates (Holzenberger et al., 2003).
  • In humans, the insulin/insulin-like growth factor signaling pathway also is involved in lifespan regulation.
  • Polymorphic variants of IGF-related pathways confer health and lifespan benefits in humans (Bonafè et al.,2003; Kojima et al., 2004; Pawlikowska et al., 2009).
  • Female Ashkenazi Jewish centenarians show an overrepresentation of loss-of-function mutations in the IGF-1 receptor (Suh et al., 2008).
  • Laron dwarves, who are growth hormone receptor deficient, have reduced levels of IGF-1, and despite being generally overweight, they have a major reduction in the risk of type 2 diabetes and cancer (Guevara-Aguirre et al., 2011; Steuerman et al., 2011).
  • People with acromegaly (due to increased growth hormone and IGF-1 production) have a two- to threefold increase in mortality, mostly because of vascular disease (Clayton, 2003).
  • Regarding the mTOR pathway, loss-of-function of mTOR or proteins involved in the mTOR pathway doubles the lifespan in the nematodeCaenorhabditis elegans (Vellai et al., 2003) and extends lifespan in the fruit fly Drosophila melanogaster (Kapahi et al., 2004).
  • Mice that express mTOR at 25% of wild-type mice display a 20% increase in median lifespan (Wu et al., 2013).
  • Rapamycine, a pharmacological mTOR inhibitor, extends lifespan with 9% in male and 14% in female mice (Harrison et al., 2009).