Carol A Shively

• Ph.D.
• Professor (Full) at Wake Forest University

INTRODUCTION Diet quality mediates aging‐related risks of cognitive decline, neurodegeneration, and Alzheimer's disease (AD) through poorly defined mechanisms. METHODS The effects of diet on the presynaptic proteome of the temporal cortex were assessed in 36 female cynomolgus macaques randomized to Mediterranean or Western diets for 31 months. Ass...

Background Older vervet monkeys are an excellent model for studying age‐associated Aß deposition; however, they have high proportions of low‐affinity Aß sites compared to human brains. Commonly used Aß PET radiotracers are most useful in detecting high affinity Aß fibrils. Measuring real‐time levels of low affinity Aß fibrils through PET provides c...

Background Diet composition is associated with neurodegenerative disease risk including Alzheimer’s Disease (AD). The adverse effects of Western‐style diets may be moderated, in part, by systemic as well as central inflammation, whereas the neuroprotective effects of Mediterranean diets may work through mechanisms that promote anti‐inflammatory phe...

Background Western and Mediterranean diets differentially affect cerebral cortical gene expression, brain structure, and socioemotional behavior in middle‐aged female nonhuman primates (NHP) (Macaca fascicularis). In this study, we investigate the effect of diet on brain molecular composition. Method Using a machine learning approach, we quantifie...

Background Mediterranean diets may reduce Alzheimer’s disease (AD) risk and preserve cognitive function relative to Western diets by protecting against inflammation. In a long term controlled randomized trial of Mediterranean vs. Western diet consumption in cynomolgus macaques (Macaca fascicularis), difficult to conduct in humans, we found signific...

Age-associated loss of muscle mass and function and subsequent mobility decline define poor health outcomes, reduced quality of life, and mortality risk. The rate and extent of aging-related muscle loss varies across older adults. It is challenging to understand the molecular pathogenesis of mobility decline, as anthropometric and imaging technique...

Background Older vervet monkeys are an excellent model for studying age‐associated Aβ deposition; however, they have high proportions of low‐affinity Aβ sites compared to human brains. Commonly used Aβ PET radiotracers are most useful in detecting high affinity Aβ fibrils. Measuring real‐time levels of low affinity Aβ fibrils through PET provides c...

There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Sex-specific Kaplan–Meier survival curves were computed in 12 translational aging models: baboon, bonnet macaque, chimpanzee, common marmoset, coppery titi monkey, co...

Importance Alzheimer’s disease (AD) is the most common cause of dementia in the elderly with the incidence rising exponentially after the age of 65 years. Unfortunately, effective treatments are extremely limited and definite diagnosis can only be made at autopsy. This is in part due to our limited understanding of the complex pathophysiology, incl...

There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Sex-specific Kaplan-Meier survival curves were computed in 12 translational aging models: baboon, bonnet macaque, chimpanzee, common marmoset, coppery titi monkey, co...

Background Western vs. Mediterranean patterned diets have been associated with divergent effects on neurodegenerative diseases including Alzheimer’s Disease (AD). Such effects may be mediated through the gut microbiome, although the exact mechanisms linking diet, microbiome, and brain outcomes remain unclear. Oscillospira, a genus of gut‐dwelling b...

Background In humans, social integration wanes with age, a pattern hypothesized to stem from cognitive or physical decrements. Social isolation increases dementia risk. Nonhuman primates provide important translational opportunities to study brain‐body relationships that may promote healthy or pathological aging. Vervet monkeys ( Chlorocebus sabaeu...

Background Mediterranean diets may reduce Alzheimer’s disease (AD) risk and preserve cognitive function relative to Western diets in part by protecting against neuroinflammation. In middle‐aged humans that subsequently develop AD, increased cortical thickness precedes atrophy. It is hypothesized that the initial increase in brain volumes may be due...

Background Mediterranean diets may reduce Alzheimer’s disease (AD) risk and preserve cognitive function relative to Western diets in part by protecting against neuroinflammation. In middle‐aged humans that subsequently develop AD, increased cortical thickness precedes atrophy. It is hypothesized that the initial increase in brain volumes may be due...

Nonhuman primates (NHPs) are valuable models for studying healthspan, including frailty development. Frailty metrics in people centers on functional measures, including usual gait speed which can be predictive of all‐cause mortality. This concept that physical competencies are able to prognosticate an individual's health trajectory over chronologic...

INTRODUCTION Mediterranean diets may be neuroprotective and prevent cognitive decline relative to Western diets, however the underlying biology is poorly understood. METHODS We assessed the effects of Western vs. Mediterranean-like diets on RNAseq generated transcriptional profiles in temporal cortex and their relationships with changes in MRI neu...

Debate exists on life-course adrenocortical zonal function trajectories. Rapid, phasic blood steroid concentration changes, such as circadian rhythms and acute stress responses, complicate quantification. To avoid pitfalls and account for life-stage changes in adrenocortical activity indices, we quantified zonae fasciculata (ZF) and reticularis (ZR...

Comparing brain structure across species and regions enables key functional insights. Leveraging publicly available data from a novel mass cytometry-based method, synaptometry by time of flight (SynTOF), we applied an unsupervised machine learning approach to conduct a comparative study of presynapse molecular abundance across three species and thr...

ДОГОВОР ЦЕЛЕВОГО КОММЕРЧЕСКОГО ФИНАНСИРОВАНИЯ БЕЗ НОМЕРА ОТ 29 НОЯБРЯ 2017 ГОДА.

Social disadvantage and diet composition independently impact myriad dimensions of health. They are closely entwined, as social disadvantage often yields poor diet quality, and may interact to fuel differential health outcomes. This paper reviews effects of psychosocial stress and diet composition on health in nonhuman primates and their implicatio...

29 июня 2023 года Ключевые слова. Новости современной психиатрии всегда вызывают интерес и обсуждения. Среди ключевых слов, которые вы указали, есть такие понятия, как природа, материя, фармакология, помощь и физический организм. Давайте рассмотрим некоторые аспекты, которые связаны с этими ключевыми словами. В последние годы было предложено неско...

Background G‐protein‐coupled receptors (GPCRs) plays a key role in regulating glucose metabolism. While GPR119 (an important GPCR) agonists have shown potential for improving neurologic and cognitive function in patients with AD and type2 diabetes mellitus (T2DM), clinical interventions targeting GPR119 will require accurate in vivo measures such a...

Background Psychosocial stress is associated with micro‐ and macrostructural brain changes that may increase risk of Alzheimer’s disease (AD). White matter (WM) appears particularly vulnerable, and changes in white matter integrity are an early sign of AD pathogenesis. Cynomolgus macaques (Macaca fascicularis) have complex central nervous systems a...

In humans, social participation and integration wane with advanced age, a pattern hypothesized to stem from cognitive or physical decrements. Similar age-related decreases in social participation have been observed in several nonhuman primate species. Here, we investigated cross-sectional age-related associations between social interactions, activi...

Ovarian dysfunction increases risk for chronic diseases of aging including cardiovascular disease, depression, cognitive impairment, as well as bone and muscle loss which promote frailty. Psychosocial stress can disrupt ovarian function, and recent observations suggest that consumption of a Western Diet may also. Determination of causal relationshi...

G‐protein‐coupled receptors (GPCRs) plays a key role in regulating glucose metabolism. While GPR119 (an important GPCR) agonists have shown potential for improving neurologic and cognitive function in patients with AD and type2 diabetes mellitus (T2DM), clinical interventions targeting GPR119 will require accurate in vivo measures such as PET imagi...

Psychosocial stress is associated with micro‐ and macrostructural brain changes that may increase risk of Alzheimer’s disease (AD). White matter (WM) appears particularly vulnerable, and changes in white matter integrity are an early sign of AD pathogenesis. Cynomolgus macaques (Macaca fascicularis) have complex central nervous systems and naturall...

We previously demonstrated in non-human primates (NHP) that Mediterranean diet consumption shifted the proportional abundance of Lactobacillus in the breast and gut. This data highlights a potential link about gut-breast microbiome interconnectivity. To address this question, we compared bacterial populations identified in matched breast and faecal...

The prefrontal cortex (PFC) is central to working memory, temporal processing, decision making, flexibility, and goal-oriented behavior, and has been implicated as a key brain region responsible for age-related cognitive decline. Although studies in humans and multiple nonhuman primate (NHP) species have shown reduction of PFC activity associated w...

Introduction: Olfactory impairment in older individuals is associated with an increased risk of Alzheimer's disease (AD). Characterization of age versus neuropathology-associated changes in the brain olfactory pathway may elucidate processes underlying early AD pathogenesis. Here, we report age versus AD neuropathology–associated differential trans...

Dietary composition is associated with the differential prevalence of psychiatric disorders; the Western diet confers increased risk, while the Mediterranean diet appears to reduce risk. In nonhuman primates, anxiety-like behaviors and social isolation have been linked to both Western diet consumption and increased inflammatory disease risk, and re...

Introduction: Age-related neuropathology associated with sporadic Alzheimer's disease (AD) often develops well before the onset of symptoms. Given AD's long preclinical period, translational models are needed to identify early signatures of pathological decline. Methods: Using structural magnetic resonance imaging and cognitive assessments, we e...

Chronic psychosocial stress is associated with increased risk of many chronic diseases including type 2 diabetes mellitus. However, it is difficult to establish a causal relationship between stress and diabetes in human studies because stressors often are self-reported and may be distant in time from metabolic consequences. Macaques are useful mode...

Synaptic molecular characterization is limited for Alzheimer’s disease (AD). Our newly invented mass cytometry–based method, synaptometry by time of flight (SynTOF), was used to measure 38 antibody probes in approximately 17 million single-synapse events from human brains without pathologic change or with pure AD or Lewy body disease (LBD), nonhuma...

Age-related changes in DNA methylation are potent regulators of gene expression and may in part explain the onset of disease and disability. Vervet monkeys are a well-described model of neurocognitive and physical aging. Like humans, gait speed declines with age in vervets, and variability in gait speed in older animals is associated with age-relat...

Ovarian dysfunction increases risk for chronic diseases of aging including cardiovascular disease, depression, cognitive impairment, and bone and muscle loss which promote frailty. Psychosocial stress disrupts ovarian function and recent observations suggest that Western diet may also. Determination of causal relationships among diet, psychosocial...

Background Microtubule (MT) integrity is critical for cell function and viability. Abnormal MT stability is commonly attributed to hyperphosphorylation of the MT‐associated protein, tau. However, the time course of MT instability in disease progression remains unknown. In vivo MT imaging offers an opportunity to gain critical information on MT chan...

Background Mounting evidence suggests that diet may influence risk for cognitive impairment and neurodegenerative disease, including Alzheimer’s disease. Nonhuman primates are important models of cognitive aging and Alzheimer’s disease‐like neuropathology given their complex central nervous systems and susceptibility to diet‐induced diseases. Diffu...

Background Age‐related neurodegeneration characteristic of late‐onset Alzheimer’s disease (LOAD) begins in middle age, well before symptoms. Therefore, translational models to identify modifiable risk factors in middle‐age are needed to understand the etiology and identify early therapeutic targets for intervention. Vervet monkeys ( Chlorocebus aet...

Background Microtubule (MT) integrity is critical for cell function and viability. Abnormal MT‐stability in AD is commonly attributed to hyperphosphorylation of the MT‐associated protein, tau. However, the time course of MT instability in disease progression remains unknown. In vivo MT imaging offers an opportunity to gain critical information on M...

Mitochondrial dysfunction is evident in diseases affecting cognition and metabolism such as Alzheimer's disease and type 2 diabetes. Human studies of brain mitochondrial function are limited to post-mortem tissue, preventing the assessment of bioenergetics by respirometry. Here, we investigated the effect of two diets on mitochondrial bioenergetics...

Western diets increase the prevalence of chronic diseases. Peripheral blood monocytes, macrophage precursors and important mediators of innate immunity and inflammation, are sensitive to the environment and may be a critical pathway linking diet to disease. We determined effects of 15 months of Western or Mediterranean diet on monocyte polarization...

Dietary changes associated with industrialization increase the prevalence of chronic diseases, such as obesity, type II diabetes, and cardiovascular disease. This relationship is often attributed to an ‘evolutionary mismatch’ between human physiology and modern nutritional environments. Western diets enriched with foods that were scarce throughout...

AMP-activated protein kinase (AMPK) is a molecular sensor that is critical for the maintenance of cellular energy homeostasis, disruption of which has been indicated in multiple neurodegenerative diseases including Alzheimer's disease (AD). Mammalian AMPK is a heterotrimeric complex and its enzymatic α subunit exists in two isoforms: AMPKα1 and AMP...

Aging across the Primate Order is poorly understood because ages of individuals are often unknown, there is a dearth of aged animals available for study, and because aging is best characterized by longitudinal studies which are difficult in long-lived species. The human population is aging rapidly, and advanced age is a primary risk factor for seve...

Synaptic molecular characterization is limited for Alzheimers disease (AD). We used mass cytometry to quantify 38 probes in approximately 17 million single synaptic events from human brains without pathologic change or with pure AD or Lewy body disease (LBD), non-human primates (NHP), and PS/APP mice. Synaptic molecular integrity in humans and NHP...

Background The objective of this study was to increase understanding of the complex interactions between diet, obesity, and the gut microbiome of adult female non-human primates (NHPs). Subjects consumed either a Western (n=15) or Mediterranean (n=14) diet designed to represent human dietary patterns for 31 months. Body composition was determined u...

Age‐related neurodegeneration characteristic of late‐onset Alzheimer's disease (LOAD) begins in middle age, well before symptoms. Translational models to identify modifiable risk factors are needed to understand etiology and identify therapeutic targets. Here, we outline the evidence supporting the vervet monkey (Chlorocebus aethiops sabaeus) as a...

Dual declines in gait speed and cognitive performance are associated with increased risk of developing dementia. Characterizing the patterns of such impairments therefore is paramount to distinguishing healthy from pathological aging. Nonhuman primates such as vervet/African green monkeys (Chlorocebus aethiops sabaeus) are important models of human...

A Correction to this paper has been published: https://doi.org/10.1038/s41398-021-01251-8

Adolescent depression is a common and serious mental disorder with unique characteristics that are distinct from adult depression. The adult non-human primate stress-induced model of depressive-like behavior is an excellent model for the study of mechanisms; however, an adolescent nonhuman primate model is still lacking. Ten male adolescent cynomol...

Age-related neurodegeneration associated with Alzheimer’s (AD) disease begins in middle age, well before the onset of symptoms. Therefore, translational models to identify modifiable risk factors in middle-age are needed to understand etiology and identify therapeutic targets. Vervet monkeys (Chlorocebus aethiops sabaeus), like humans, naturally de...

Diet may influence the risk for cognitive decline and neurodegenerative disorders, including Alzheimer’s disease (AD), but these relationships are difficult to study in humans. Cynomolgus macaques (Macaca fascicularis) are appropriate models for investigations of diet effects on the brain because, like humans, they are omnivorous, have complex cent...

Introduction: Associations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer's disease (AD), have been reported, but causal relationships are difficult to determine in human studies. Methods: We used structural magnetic resonance imaging in a well-validated non-human primate model of AD-like neuropathology to...

Background Associations between diet, cognitive decline and neurodegenerative disease, including Alzheimer’s Disease (AD), have been reported, but whether these relationships are causal is difficult to determine in human studies. Cynomolgus macaques ( Macaca fascicularis ), like humans, are omnivorous, have complex central nervous systems, and are...

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 s...

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 s...

INTRODUCTION Associations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer’s disease (AD), have been reported, but causal relationships are difficult to determine in human studies. METHODS We used structural magnetic resonance imaging in a well-validated nonhuman primate model of AD-like neuropathology to exami...

Objectives Poor diet and obesity often go hand-in-hand and are difficult to discern which variable is the major driver of the gut microbiome. The objective of this study was to determine the impact of obesity within dietary exposures on the gut microbiome and metabolic parameters using a non-human primate model. Methods Female M. fasicularis monke...

Social animals need connection Much research over the past decade or so has revealed that health and lifespan in humans, highly social animals, are reduced with social adversity. We humans are not the only animals that are social, however, and similar research has shown that other social mammals are similarly influenced by isolation and adversity....

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 physiolog...

Social status is a powerful correlate of aging-related health decline. Observational data in humans suggest that disadvantaged social status may be associated with accelerated biological aging. But establishing causality in this relationship poses challenges; experimental manipulation of human social status is not possible. In contrast, social stat...

Diet modifications are some of the most well-established aging interventions. For decades we have known that caloric restriction can dramatically increase lifespan and healthspan in organisms ranging from yeast to primates. More recently, other dietary modifications, including varying nutrient composition, have been experimentally shown to alter he...

Objective: Our institutional Women in Medicine & Science Program (formerly the Office of Women in Medicine and Science) developed the Early Career Development Program for Women to promote the careers of women faculty. At 6 monthly sessions, participants learn relevant content (imposter syndrome, strengths, change style, career management, assertiv...

The gut microbiota plays a fundamental role in host health and disease. Host diet is one of the most significant modulators of the gut microbial community and its metabolic activities. Evidence demonstrates that dietary patterns such as the ‘Western diet’ and perturbations in gut microbiome (dysbiosis) have strong associations with a wide range of...

Background: Western diets are associated with increased incidences of obesity, hypertension, diabetes, and hypercholesterolemia, whereas Mediterranean diets, richer in polyphenols, monounsaturated fats, fruits, vegetables, poultry, and fish, appear to have cardiometabolic health benefits. Previous work has included population-based studies with li...

Gut microbiome plays a fundamental role in several aspects of host health and diseases. There has been an exponential surge in the use of animal models that can mimic different phenotypes of the human intestinal ecosystem. However, data on host species-specific signatures of gut microbiome and its metabolites like short-chain fatty acids (SCFAs; i....

Introduction Nonhuman primates may serve as excellent models of sporadic age-associated brain β-amyloid deposition and Alzheimer’s disease pathologic changes. We examined whether a vervet nonhuman primate model recapitulated pathologic, physiologic, and behavioral features of early Alzheimer’s disease. Methods Nine middle-aged (mean = 11.2 years)...

Background Left ventricular (LV) diastolic dysfunction often precedes heart failure with preserved ejection fraction, the dominant form of heart failure in postmenopausal women. The objective of this study was to determine the effect of oral estradiol treatment initiated early after ovariectomy on LV function and myocardial gene expression in femal...

Recent identification of a mammary gland-specific microbiome led to studies investigating bacteria populations in breast cancer. Malignant breast tumors have lower Lactobacillus abundance compared with benign lesions, implicating Lactobacillus as a negative regulator of breast cancer. Diet is a main determinant of gut microbial diversity. Whether d...

Introduction Depressive symptoms (DS) in humans are associated with decreased resting state vagal activity, but sex seems to moderate this association. Recently, in human females DS have been associated with greater or similar cardiac vagal activity compared to men in both, clinical and non-clinical samples. A previously validated animal model of b...

Depression is the most common mental health problem in aging persons and is a leading risk factor for physical disability, especially in women. Though antidepressant drugs such as serotonin reuptake inhibitors (SSRI) are commonly prescribed, epidemiological evidence reveals mixed effects of long-term antidepressant use on physical function and acti...

Blood-based bioenergetic profiling provides a minimally invasive assessment of mitochondrial health shown to be related to key features of aging. Previous studies show that blood cells recapitulate mitochondrial alterations in the central nervous system under pathological conditions, including the development of Alzheimer’s disease. In this study o...

Objective: Atherosclerosis developed during premenopausal years predicts postmenopausal atherosclerosis burden. Selective serotonin reuptake inhibitor (SSRI) antidepressants, recently approved for hot flushes, have been associated with increased ischemic stroke risk in several observational studies; however, effects on carotid artery atheroscleros...

Cognitive impairment in older individuals is a complex trait that in population-based studies most commonly derives from an individually varying mixture of Alzheimer disease, Lewy body disease, and vascular brain injury. We investigated the molecular composition of synaptic particles from three sources: consecutive rapid autopsy brains from the adu...

Selective serotonin reuptake inhibitor (SSRI) use is ubiquitous because they are widely prescribed for a number of disorders in addition to depression. Depression increases the risk of coronary heart disease (CHD). Hence, treating depression with SSRIs could reduce CHD risk. However, the effects of long term antidepressant treatment on CHD risk, as...

Depression is a common and debilitating mood disorder that impacts women more often than men. The mechanisms that result in depressive behaviors are not fully understood; however, the hippocampus has been noted as a key structure in the pathophysiology of depression. In addition to neural implications of depression, the cardiovascular system is imp...

Intestinal barrier dysfunction leads to microbial translocation (MT) and inflammation in vertebrate and invertebrate animal models. Age is recently recognized as a factor leading to MT, and in some human and animal model studies, MT was associated with physical function. We evaluated sarcopenia, inflammation, MT biomarkers, and muscle insulin sensi...