Biology subjects

Appt, S. E.

Publications and source records attributed to Appt, S. E..

3 recordsLinked to original sources

bioRxiv2020

Mediterranean Diet, Stress Resilience, and Aging in Nonhuman Primates

Persistent psychological stress increases the risk of many chronic diseases of aging. Little progress has been made to effectively reduce stress responses or mitigate stress effects suggesting a need for better understanding of factors that influence stress responses. Limited evidence suggests that diet may be a factor in modifying the effects of stress. However, long-term studies of diet effects on stress reactive systems are not available, and controlled randomized clinical trials are difficult and costly. Here we report the outcomes of a controlled, randomized preclinical trial of the effects of long-term consumption (31 months, [~] equivalent to 9 human years) of Western versus Mediterranean - like diets on behavioral and physiological responses to acute (brief social separation) and chronic (social subordination) psychosocial stress in 38 adult, socially-housed, female cynomolgus macaques. Compared to animals fed a Western diet, those fed the Mediterranean diet exhibited enhanced stress resilience as indicated by lower sympathetic activity, brisker and more overt heart rate responses to acute stress, more rapid recovery, and lower cortisol responses to acute psychological stress and adrenocorticotropin (ACTH) challenge. Furthermore, age-related increases in sympathetic activity and cortisol responses to stress were delayed by the Mediterranean diet. Population level diet modification in humans has been shown to be feasible. Our findings suggest that population-wide adoption of a Mediterranean-like diet pattern may provide a cost-effective intervention on psychological stress and promote healthy aging with the potential for widespread efficacy. HighlightsO_LIThere is no population level treatment to reduce stress and associated disease. C_LIO_LIMediterranean diet reduced sympathetic activity. C_LIO_LIMediterranean diet reduced cortisol response to acute stress and to ACTH challenge. C_LIO_LIMediterranean diet delayed age-related increases in sympathetic activity and cortisol responses to stress. C_LIO_LIThese results suggest a dietary strategy to increase stress resilience. C_LI

physiology↗

bioRxiv2020

Diet, psychosocial stress, and Alzheimer's disease-related neuroanatomy in female nonhuman primates

INTRODUCTIONAssociations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimers disease (AD), have been reported, but causal relationships are difficult to determine in human studies. METHODSWe used structural magnetic resonance imaging in a well-validated nonhuman primate model of AD-like neuropathology to examine the longitudinal effects of diet (Mediterranean versus Western) and social subordination stress on brain anatomy, including global volumes, cortical thicknesses and volumes, and twenty individual regions of interest (ROIs). RESULTSWestern diet resulted in greater cortical thicknesses, total brain volumes and gray matter, and diminished cerebrospinal fluid and white matter volumes. Socially stressed subordinates had smaller whole brain volumes but larger ROIs relevant to AD than dominants. DISCUSSIONThe observation of increased size of AD-related brain areas is consistent with similar reports of mid-life volume increases predicting increased AD risk later in life. While the biological mechanisms underlying the findings require future investigation, these observations suggest that Western diet and psychosocial stress instigate pathologic changes that increase risk of AD-associated neuropathologies, whereas Mediterranean diet may protect the brain. RESEARCH IN CONTEXTO_LISystematic review: The authors reviewed the literature with PubMed and Google Scholar and found a number of publications which are cited that suggest that AD pathogenesis begins well before the onset of symptoms. C_LIO_LIInterpretation: Our findings support the hypothesis that Western diet and psychosocial stress may instigate neuroinflammatory responses that increase risk of later developing AD-like neuropathologies, whereas the structural stasis in the Mediterranean diet group may represent a resilient phenotype. C_LIO_LIFuture directions: The manuscript serves as a critical first step in describing risk and resilient phenotypes during middle age in a nonhuman primate model of AD-like neuropathology. This report lays the groundwork for ongoing efforts to determine whether neuroinflammatory profiles differed across diet and stress groups. Future studies should aim to understand the temporal emergence of functional disparities associated with the changes in brain structure observed here. C_LI HIGHLIGHTSO_LIGlobal brain volumes changed in response to Western, but not Mediterranean, diet. C_LIO_LIWestern diet increased cortical thickness in multiple regions relevant to AD. C_LIO_LIMediterranean diet did not alter cortical thicknesses relevant to AD. C_LIO_LIBrain regions associated with AD risk differed between low and high stress monkeys. C_LIO_LIPsychosocial stress may modulate the effects of diet on the brain. C_LI

neuroscience↗

bioRxiv2020

Divergent effects of Western and Mediterranean diets on behavior and monocyte polarization.

Dietary changes associated with industrialization substantially increase the prevalence of chronic diseases, such as obesity, type II diabetes, and cardiovascular disease, which are major contributors to the public health burden. The high prevalence of these chronic diseases is often attributed to an "evolutionary mismatch," between human physiology and modern nutritional environments. In support of this idea, Western diets enriched with foods that were scarce throughout human evolutionary history (e.g., simple sugars and saturated fats) promote inflammation and disease relative to diets more akin to hunter-gatherer diets, such as a Mediterranean diet; however, the mechanisms linking dietary mismatch to inflammation and chronic disease are poorly understood. We used a macaque model and whole diet manipulations to evaluate one possible mechanism - inflammatory polarization of monocytes - that potentially leads to this evolutionary mismatch. After consuming a Western- or Mediterranean-like diet for 15 months, monocytes from Western diet consumers exhibited a more proinflammatory phenotype, with 40% of their genes differentially expressed (FDR<0.05). Compared to the Mediterranean diet, the Western diet shifted the co-expression of 445 gene pairs, including small RNAs and transcription factors associated with metabolism and adiposity in humans, and dramatically altered animal behavior. For example, Western-fed individuals were more anxious and less socially integrated compared to the Mediterranean-fed subjects. These behavioral changes were also associated with some of the effects of diet on gene expression, suggesting an interaction between diet, central nervous system activity, and monocyte gene expression. The results of this study provide new insights into evolutionary mismatch at the molecular level and uncover new pathways through which Western diets generate inflammation and disease.

genomics↗