Beyond Diabetes: Does Obesity-Induced Oxidative Stress Drive the Aging Process?

Adam Salmon

doi:10.3390/antiox5030024

Abstract

Despite numerous correlative data, a causative role for oxidative stress in mammalian longevity has remained elusive. However, there is strong evidence that increased oxidative stress is associated with exacerbation of many diseases and pathologies that are also strongly related to advanced age. Obesity, or increased fat accumulation, is one of the most common chronic conditions worldwide and is associated with not only metabolic dysfunction but also increased levels of oxidative stress in vivo. Moreover, obesity is also associated with significantly increased risks of cardiovascular disease, neurological decline and cancer among many other diseases as well as a significantly increased risk of mortality. In this review, we investigate the possible interpretation that the increased incidence of these diseases in obesity may be due to chronic oxidative stress mediating segmental acceleration of the aging process. Understanding how obesity can alter cellular physiology beyond that directly related to metabolic function could open new therapeutic areas of approach to extend the period of healthy aging among people of all body composition.

Highlights

A large number of diseases, pathologies and other maladies become much more prevalent with advanced age
The most well-known physiological defect associated with obesity is the development of metabolic disorders, including and primarily type 2 diabetes mellitus (T2DM)
We have previously shown that in vivo oxidative damage is significantly elevated in high fat fed, obese mice to a degree roughly equivalent to the increase in oxidative damage associated with old age [15]

Summary

Introduction

A large number of diseases, pathologies and other maladies become much more prevalent with advanced age. Thorough literature searches published elsewhere show for the most part that aging is associated with accumulation of oxidative damage to cellular macromolecules, reduced antioxidant defenses and increased susceptibility to oxidative stress in vivo [4,5] These findings have generally held true for multiple organisms tested including standard invertebrate and vertebrate laboratory models, wild-caught organisms and human populations. Digging deeper into other antioxidant mutant mouse models more generally, there is sufficient evidence to suggest that altering the accumulation of oxidative stress/damage does often correlate with changes in health associated with age if not longevity itself [14,15]. If we could control the source of stress sufficiently, this could be used to determine (1) if these external variables really affect the aging rate or only the development of diseases that limit lifespan and (2) what role oxidative stress plays in the process. Rather than trying to identify vague sources of stress that may exist between animal vivaria, or between the laboratory and the real world, we propose inducing low-level, chronic stress by promoting obesity and metabolic dysfunction using high fat diets for reasons described below

Obesity and Oxidative Stress

Obesity and Decline in Health Span

Conclusions