The Microbiome of Aging and Age-Related Disease

Abstract

With a rising prevalence of obesity (defined as BMI≥30) among all age groups in the United States, there is a serious concern on the long-term effects of excess fat. Obesity dramatically increases the likelihood of mortality and the risk of several chronic illnesses such as cardiovascular disease, diabetes, and cancer leading some to suggest that this condition is representative of accelerated aging. In this study, we tested two fundamental questions: 1) does consumption of a high fat diet throughout adulthood limit life span and 2) does obesity accelerate declines in physiological function associated with aging? To address these questions, we monitored C57BL/6J mice that were fed a high fat diet starting in adulthood (8 months of age) until the end of their natural life. As predicted, we found that obesity was associated with changes in metabolic function consistent with increased caloric consumption. Furthermore, mortality was significantly increased in high fat-fed mice such that the life span of obese mice was reduced ~25% compared to their lean, standard chow-fed counterparts. All mice in this study underwent a comprehensive analysis of different markers of functional performance in assays designed to assess co-ordination, muscle function, activity and mobility, cognition, and sleep patterns. Mice were assessed longitudinally with an initial assessment after a short period of high fat feeding (4 months/12 months of age) as well after a long-term period of feeding (10 months/18 months of age). We also found evidence suggesting that obesity altered the dynamics of normal age-related changes in most of these parameters such that factors were significantly worsened in high fat-fed mice even after statistical correction for increased body weight, adiposity, and metabolic dysfunction. These data then suggest that the cellular mechanisms that cause these declines may be exacerbated by obesity. Overall, these data suggest that lifelong obesity does accelerate some aspects of the aging process and that targeting the reduction of oxidative stress may have therapeutic potential to benefit those most at risk.