Dorothy Sears

• PhD
• Professor at Arizona State University

Introduction Cognitive decline and sleep concerns are significant health issues among older adults. Nonpharmacological treatments to address these concerns are needed, particularly for older adults who are more likely to be prescribed multiple medications and experience adverse effects of additional drugs. The aim of the current qualitative study w...

Postprandial hyperglycemia, marked by the blood glucose level exceeding the normal range after meals, is a critical indicator of progression toward type 2 diabetes in prediabetic and healthy individuals. A key metric for understanding blood glucose dynamics after eating is the postprandial area under the curve (PAUC). Predicting PAUC in advance bas...

Background: Incidence of cardiometabolic disease among U.S. Hispanics/Latinos is higher than in non-Hispanic Whites. Prolonged sitting duration is prevalent in older adults, and compounded with menopause, greatly increases cardiometabolic risk in postmenopausal women. Metabolomic analyses of interventions to reduce sitting are lacking and mechanist...

Background Disruption of sleep and circadian rhythms are associated with cognitive decline, preclinical Alzheimer’s Disease (AD) pathology, and increased risk of dementia. Alleviating circadian rhythm and sleep disruption may improve cognition and reduce the progression of AD and related dementias (ADRD). Time‐restricted eating (TRE), a circadian b...

Purpose The association between cardiovascular health (CVH) with perceived quality of life (PQoL) and variations by sex and Hispanic ethnicity is not well understood. Methods This study included 583 participants (42% Hispanic, 56% female, mean age 59 years). Linear regression modeled the covariate-adjusted associations between CVH, using the combi...

Introduction Older age significantly increases risk for cognitive decline. A growing number of older adults (≥ 65 years) experience cognitive decline that compromises immediate and/or long-term health. Interventions to mitigate cognitive decline are greatly needed. Intermittent fasting aligned with innate circadian rhythms is associated with health...

Objective/Goals Cognitive decline is intricately linked to various factors such as obesity, stress, poor sleep, and circadian rhythm misalignment, which are interrelated in their impact on cognitive health. Irregular food-intake timing further compounds these issues. The practice of prolonged nightly fasting (PNF) may help synchronize food intake w...

Older adults sit during most hours of the day; more than 30% are considered physically inactive. The accumulation of prolonged sitting time is an exercise-independent risk factor for aging-related conditions such as cardiometabolic disease and cancer. Archival plasma samples from a randomized controlled, four-condition crossover study conducted in...

Introduction Cognitive decline is a significant, persistent issue among breast cancer survivors (BCSs) affecting more than 50% and greatly impacting health and wellbeing, particularly among those who are aging. Scalable, lifestyle interventions to mitigate cognitive decline in this population are needed. This study aimed to explore the effects of T...

Background Sedentary behavior has been identified as a significant risk factor for Metabolic Syndrome (MetS). However, it is unclear if the sedentary pattern measurement approach (posture vs. movement) impacts observed associations or if associations differ for Hispanic/Latino communities, who have higher risk of MetS. Methods Participants from th...

Introduction Growing evidence exists that greenspace exposure can reduce metabolic syndrome risk, a growing public health concern with well-documented inequities across population subgroups. We capitalize on the use of g-computation to simulate the influence of multiple possible interventions on residential greenspace on nine metabolic biomarkers a...

Chrononutrition is a rapidly evolving field of nutritional epidemiology that addresses the complex relationship between temporal eating patterns, circadian rhythms, and metabolic health, but most prior research has focused on the cardiometabolic consequences of time-restricted feeding and intermittent fasting. The purpose of this topical review is...

Background Many tumors contain hypoxic microenvironments caused by inefficient tumor vascularization. Hypoxic tumors have been shown to resist conventional cancer therapies. Hypoxic cancer cells rely on glucose to meet their energetic and anabolic needs to fuel uncontrolled proliferation and metastasis. This glucose dependency is linked to a metabo...

The gut microbiome (GM) modulates body weight/composition and gastrointestinal functioning; therefore, approaches targeting resident gut microbes have attracted considerable interest. Intermittent fasting (IF) and protein pacing (P) regimens are effective in facilitating weight loss (WL) and enhancing body composition. However, the interrelationshi...

Postmenopausal Hispanic/Latina (N = 254) women with a body mass index (BMI) ≥ 25 kg/m² were randomized to an intervention to reduce sitting time or a comparison condition for 12 weeks. The standing intervention group received three in-person health-counseling sessions, one home visit, and up to eight motivational interviewing calls. The heart healt...

Introduction Cancer related cognitive decline is a common long-term side effect of cancer and its treatments among breast cancer survivors. Physical activity is a modifiable risk factor related to cognitive decline. However, existing research lacks consensus regarding the relationship between cognition and exercise as well as the impact of cancer t...

OBJECTIVES/GOALS: Cognitive decline is associated with obesity, stress, poor sleep, and circadian rhythm misalignment, which are themselves functionally intertwined. Irregular food intake timing exacerbates these all. Prolonged nightly fasting (PNF) aligns food intake with innate circadian rhythms. METHODS/STUDY POPULATION: A nationwide, remotely-d...

Purpose We investigated the effect of metformin and lifestyle intervention on metabolic, inflammatory, and steroid biomarkers of breast cancer (BC) recurrence risk in two intervention trials among BC survivors with overweight or obesity. Methods Baseline and follow-up serum samples collected during the two trials were analyzed and data pooled. The...

Intermittent fasting (IF) and caloric restriction (CR) are dietary strategies to prevent and attenuate obesity associated with conditions and aging-related outcomes. This scoping review examined the cardiometabolic, cancer, and neurocognitive outcome differences between IF and CR interventions among adults. We applied a systematic approach to scope...

Study Objectives Examining multiple dimensions of sleep health may better capture associations between sleep and health risks, including cardiometabolic disease (CMD). Hispanics have elevated risk for inadequate sleep and CMD biomarkers. Few studies have explored whether associations between sleep and CMD differ by Hispanic ethnicity. Methods Leve...

BACKGROUND Many tumors contain hypoxic microenvironments caused by inefficient tumor vascularization. Hypoxic tumors have been shown to resist conventional cancer therapies. Hypoxic cancer cells rely on glucose to meet their energetic and anabolic needs to fuel uncontrolled proliferation and metastasis. This glucose dependency is linked to a metabo...

Objectives Weight gain and unfavorable body composition are prevalent among midlife/older women throughout menopause. These shifts may negatively impact health, well-being, and longevity. Efforts to attenuate weight and body composition changes are traditionally driven by manipulation of diet and/or exercise; however, sustained results are limited,...

Background Metformin reduces the incidence of breast cancer in patients with type 2 diabetes and obesity. However, our knowledge about the effects of metformin on cancer recurrence in breast tissue is limited. Therefore, in this study, we examined the breast tissue gene expression changes by metformin in breast cancer survivors. Methods Within the...

Significant human gut microbiome changes during adolescence suggest that microbial community evolution occurs throughout important developmental periods including the transition to college, a typical life phase of weight gain. In this observational longitudinal study of 139 college freshmen living in on-campus dormitories, we tracked changes in the...

Adipocyte dysregulation is one mechanism linking overweight and breast cancer recurrence. Exercise and weight loss are associated with a decreased risk of breast cancer recurrence in breast cancer survivors with overweight or obesity, which may be mediated through reduced leptin levels, increased adiponectin levels, and an elevated adiponectin to l...

Background Obesity is an established, modifiable risk factor of multiple myeloma (MM); yet, no lifestyle interventions are routinely recommended for patients with overweight or obesity with MM precursor conditions. Prolonged nightly fasting is a simple, practical dietary regimen supported by research, suggesting that the synchronization of feeding-...

BACKGROUND Obesity is an established, modifiable risk factor of multiple myeloma (MM); yet, no lifestyle interventions are routinely recommended for patients with overweight or obesity with MM precursor conditions. Prolonged nightly fasting is a simple, practical dietary regimen supported by research, suggesting that the synchronization of feeding-...

Introduction Postmenopausal women are particularly vulnerable to metabolic dysfunction. Compelling evidence suggests that this is due to their lacking the protective effect of estrogens. We have shown that circulating estrogens regulate daily eating and sleep-activity rhythms in female mice and protect them from obesity and diabetes. However, few s...

Obesity is associated with chronic inflammation that may contribute to T2D among youth. We examined the association between inflammatory biomarkers and insulin sensitivity and β-cell function and response to lifestyle intervention among Latino youth with obesity. Latino youth (n = 64) were randomized to six months of lifestyle intervention (INT, n...

Obesity, defined as a body mass index ≥ 30 kg/m², is associated with an increased incidence of 13 cancers and increased mortality of 14 cancers (1,2). Obesity is strongly linked to poor diet and physical inactivity, which are also independent risk factors for cancer incidence and mortality (3-5). Estimates suggest that by 2030 obesity will overtake...

Intermittent fasting entails restricting food intake during specific times of day, days of the week, religious practice, or surrounding clinically important events. Herein, the metabolic and circadian rhythm mechanisms underlying the proposed benefits of intermittent fasting for the cancer population are described. We summarize epidemiological, pre...

BACKGROUND Sedentary time (e.g., sitting with low energy expenditure) is a significant cardiometabolic disease risk factor. The modern workforce spends the majority of their workday seated at a desk. Acute (1-3 days), controlled laboratory-based studies that increase brief periods of standing or moving produce promising improvements in cardiometabo...

Background Prolonged bouts of sedentary time, independent from the time spent in engaging in physical activity, significantly increases cardiometabolic risk. Nonetheless, the modern workforce spends large, uninterrupted portions of the day seated at a desk. Previous research suggests—via improved cardiometabolic biomarkers—that this risk might be a...

Background Obesity is a major health concern for breast cancer survivors, being associated with high recurrence and reduced efficacy during cancer treatment. Metformin treatment is associated with reduced breast cancer incidence, recurrence and mortality. To better understand the underlying mechanisms through which metformin may reduce recurrence,...

Aging is significantly associated with cognitive decline. A growing number of US adults ages ≥ 65 years have neurocognitive impairment resulting in compromised immediate and/or long-term health outcomes. Interventions to mitigate cognitive decline and promote healthy aging are needed. Research in intermittent fasting (IF) suggests positive health o...

Introduction: Individual behaviors in the 24h rest-activity cycle have been linked to cardiometabolic health (CMH). Studies that integrate the overall multidimensional pattern of 24-h rest-activity rhythms (RAR) and evaluate its unique relation with CMH and type 2 diabetes (T2D) are limited. Hypothesis: Disrupted RAR are associated with poorer glyc...

Accelerometers are widely used for tracking human movement and provide minute-level (or even 30 Hz level) physical activity (PA) records for detailed analysis. Instead of using day-level summary statistics to assess these densely sampled inputs, we implement functional principal component analysis (FPCA) approaches to study the temporal patterns of...

Purpose: Physical inactivity and obesity increase risk for breast cancer recurrence and cardiovascular death; inflammation is hypothesized to mediate these associations. Methods: In a 4-arm randomized controlled trial, 318 breast cancer survivors with overweight or obesity were randomized to Exercise Alone, Weight Loss Alone, Exercise plus Weigh...

Purpose of Review The goal is to examine the link between circadian rhythms and pain, which may shed further light on improving pain management strategies and preventing the development and/or worsening of chronic pain. Recent Findings In part I, we provide evidence that the rhythmicity of pain may be regulated by the central circadian clock. We a...

Accumulating evidence links cardiometabolic health with social and environmental neighborhood exposures, which may contribute to health inequities. We examined whether environmental characteristics were individually or jointly associated with insulin resistance, hypertension, obesity, type 2 diabetes, and metabolic syndrome in San Diego County, CA....

Individual sleep dimensions have been linked to cardiovascular disease (CVD) risk and cardiometabolic health (CMH), but sleep health is multifaceted. We investigated associations of a multidimensional sleep health (MDSH) score, enabling the assessment of sleep health gradients, with CVD and CMH. Participants were 4555 adults aged ≥20 years from the...

Background The timing and regularity of eating patterns could play a role in systemic inflammation, as circadian clocks responsible for daily rhythms of inflammatory signaling are entrained by food intake. Purpose To evaluate associations of intra-weekly and weekday-weekend differences in eating timing patterns with high-sensitivity C-reactive pro...

Background: Cytotoxic therapy increases the risk of clonal hematopoiesis (CH) defined by somatic mutations of cancer-associated genes in blood stem cells. CH is associated with secondary blood cancers and other adverse health events, although the minimum clone size at which these risks become evident and factors that could mitigate them are unknown...

Epidemiological studies demonstrate an association between breast cancer (BC) and systemic dysregulation of glucose metabolism. However, how BC influences glucose homeostasis remains unknown. We show that BC-derived extracellular vesicles (EVs) suppress pancreatic insulin secretion to impair glucose homeostasis. EV-encapsulated miR-122 targets PKM...

11031 Background: Given the rising prevalence of obesity, poor diet and physical inactivity, known in combination as “energy balance” or “energetics”, as well as their associations with cancer incidence and mortality, innovative research, clinical care and training of scientists are needed to lower the prevalence of these risk factors and in turn,...

Introduction: Children and adolescents with cancer report increased fatigue and decreased physical activity, introducing risk factors for chronic disease and suppressed quality of life. Research suggests an inverse relationship between fatigue and physical activity, but the biological explanation is not well understood. The purpose of this study wa...

Introduction Metabolic syndrome, a significant risk factor for cardiovascular-related mortality, is highly prevalent in people with schizophrenia (PwS). It is a leading contributor to the growing mortality gap between PwS and the general population. Hispanics/Latinos/as/x (henceforth Hispanics) with schizophrenia, are more likely to have metabolic...

Background: Pediatric obesity is characterized by an imbalance in pro- and anti-inflammatory markers that are associated with cardiometabolic diseases. Adiponectin (Adpn), an anti-inflammatory marker, is associated with insulin sensitivity, while tumor necrosis factor-alpha (TNFα) has been associated with insulin resistance among youth with obesity...

Physical activity (PA) is significantly associated with many health outcomes. The wide usage of wearable accelerometer-based activity trackers in recent years has provided a unique opportunity for in-depth research on PA and its relations with health outcomes and interventions. Past analysis of activity tracker data relies heavily on aggregating mi...

Introduction .Exposure to air pollution disproportionately affects racial/ethnic minorities that could contribute to health inequalities including metabolic disorders. However, most existing studies used a static assessment of air pollution exposure (mostly using the residential address) and do not account for activity space when modelling exposure...

Various microbial products leaked from gut lumen exacerbate tissue inflammation and metabolic disorders in obesity. Vsig4+ macrophages are key players preventing infiltration of bacteria and their products into host tissues. However, roles of islet Vsig4+ macrophages in the communication between microbiota and β cells in pathogenesis of obesity-ass...

Metformin and weight loss relationships with epigenetic age measures—biological aging biomarkers—remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese breast cancer survivors ( N = 192) assigned to metformin, placebo, weight loss with metformin, or weight loss with placebo interventions for 6...

Postmenopausal breast cancer is the most common obesity-related cancer death among women in the U.S. Insulin resistance, which worsens in the setting of obesity, is associated with higher breast cancer incidence and mortality. Maladaptive eating patterns driving insulin resistance represent a key modifiable risk factor for breast cancer. Emerging e...

Intermittent fasting (IF) is proposed to elicit beneficial effects similar to calorie restriction including reduced oxidative stress. Oxidative stress can exacerbate and/or promote the development of metabolic-related complications and is thus an important outcome of interest in relation to obesity. In this systematic review we sought to evaluate t...

Central obesity with cardiometabolic syndrome (CMS) is a major global contributor to human disease, and effective therapies are needed. Here, we show inhibiting cyclic-GMP selective phosphodiesterase-9A (PDE9-I) in both ovariectomized female or male mice suppresses pre-established severe diet-induced obesity/CMS with or without superimposed mild ca...

Background Sleep variability and social jetlag are associated with adverse cardiometabolic outcomes via circadian disruption. Variable eating patterns also lead to circadian disruption, but associations with cardiometabolic health are unknown. Methods and Results Women (n=115, mean age: 33±12 years) completed a 1‐week food record using the Automat...

Obesity-associated breast cancer recurrence is mechanistically linked with elevated insulin levels and insulin resistance. Exercise and weight loss are associated with decreased breast cancer recurrence, which may be mediated through reduced insulin levels and improved insulin sensitivity. This is a secondary analysis of the WISER Survivor clinical...

Background: The evidence linking sugar-sweetened beverage (SSB) intake and mortality risk is conflicting, and associations between various SSB subtypes and mortality remain unclear. Objective: To examine the association between baseline SSB intake, subtypes of SSB intake, and mortality risk in women. Design: Prospective cohort study. Particip...

Time spent sitting is positively correlated with endothelial dysfunction and cardiovascular disease risk. The underlying molecular mechanisms are unknown. MicroRNAs contained in extracellular vesicles (EVs) reflect cell/tissue status and mediate intercellular communication. We explored the association between sitting patterns and microRNAs isolated...

Active travel (AT) provides an opportunity to alleviate the physical inactivity and climate crises contributing to the global chronic disease burden, including cardiovascular diseases (CVD). Though AT shows promising links to reduced CVD risk, prior studies relied on self-reported AT assessment. In the present study, device-measured and self-report...

BACKGROUND Most older adults spend the majority of their waking hours sitting, which increases their risk of chronic diseases. Given the challenges many older adults face in engaging in moderate to vigorous physical activity, understanding the health benefits of decreasing sitting time and increasing the number of sit-to-stand transitions is needed...

Background Many older adults spend the majority of their waking hours sitting, which increases their risk of chronic diseases. Given the challenges that many older adults face when engaging in moderate-to-vigorous physical activity, understanding the health benefits of decreasing sitting time and increasing the number of sit-to-stand transitions is...

Calorie restriction is a primary dietary intervention demonstrated over many decades in cellular and animal models to modulate aging pathways, positively affect age-associated diseases, and, in clinical studies, to promote beneficial health outcomes. Because long-term compliance with daily calorie restriction has proven problematic in humans severa...

The Go Red for Women movement was initiated by the American Heart Association (AHA) in the early 2000s to raise awareness concerning cardiovascular disease (CVD) risk in women. In 2016, the AHA funded 5 research centers across the United States to advance our knowledge of the risks and presentation of CVD that are specific to women. This report hig...

Central obesity with cardiometabolic syndrome (CMS) is a major global contributor to human disease, and effective therapies are needed. Here, we show inhibiting cyclic-GMP selective phosphodiesterase-9A (PDE9-I) suppresses established diet-induced obesity and CMS in ovariectomized female and male mice. PDE9-I reduces abdominal, hepatic, and myocard...

Accumulating evidence indicates that obesity with its associated metabolic dysregulation, including hyperinsulinemia and aberrant circadian rhythms, increases the risk for a variety of cancers including postmenopausal breast cancer. Caloric restriction can ameliorate the harmful metabolic effects of obesity and inhibit cancer progression but is dif...

Introduction Difficulties with cognition are extremely common among breast cancer survivors and can significantly impact quality of life, daily functioning, and ability to return to work. One promising intervention is increasing physical activity, as it has been effective in improving cognition in non-cancer populations. Few physical activity inter...

Introduction: Misalignment of lifestyle behaviors with circadian rhythms is related to hypertension (HTN) risk in experimental studies. Estimation of the circadian rhythm of 24 h rest-activity patterns, which serves as a measure of circadian rhythmicity in a free-living population setting, has been linked to health outcomes but its association with...

Introduction: Social connectedness (SC) is an important determinant of maintaining overall health, and the strength of connections with others may influence cardiovascular health (CVH) in part through improvement in cardiovascular disease risk factors. However, there is a lack of research on the role of SC in promoting CVH, as defined by the Americ...

Introduction: Increased sedentary behavior is independently associated with increased risk of cardiometabolic diseases. There are few community-based RCTs designed to address this behavior, and none among Latinas, who are particularly at risk for cardiometabolic diseases. This study presents the results of an intervention to reduce sitting time amo...

Introduction: Social jet lag, typically defined as the difference in sleep timing on work vs. free days, is related to elevated cardiovascular disease (CVD) risk, via circadian disruption. Irregular meal timing may also lead to circadian disruption, but the role of social jet lag in eating patterns in CVD risk has not been examined. Hypothesis: Soc...

Nightly fasting duration (NFD) and eating timing and frequency may influence cardiometabolic health via their impact on circadian rhythms, which are entrained by food intake, but observational studies are limited. This 1-year prospective study of 116 US women (33 ± 12y, 45% Hispanic) investigated associations of habitual NFD and eating timing and f...

Background: Sedentary behavior (SB) is linked to negative health outcomes in older adults. Most studies use summary values, e.g., total sedentary minutes/day. Diurnal timing of SB accumulation may further elucidate SB-health associations. Methods: Six thousand two hundred four US women (mean age = 79 ± 7; 50% White, 34% African-American) wore ac...

Background Sugar‐sweetened beverage ( SSB ) consumption has been associated with cardiometabolic risk. However, the association between total and type of SSB intake and incident cardiovascular disease ( CVD ) end points such as myocardial infarction, stroke, and revascularization is limited. Methods and Results We examined the prospective associat...

Background and Hypothesis During waking hours, older adults spend the most time sitting and are least likely to meet physical activity guidelines. Such a sedentary lifestyle is associated with cardiovascular and coronary heart disease mortality risk, particularly in postmenopausal Hispanic/Latino women. The deleterious impact of prolonged sitting i...

Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with c...

Purpose of Review Disparities in prevalence of obesity in the USA continue to increase. Here, we review progress and highlight gaps in understanding disparities in obesity with a focus on the Hispanic/Latino population from a systems epidemiology framework. We review seven domains: environment, behavior, biomarkers, nutrition, microbiome, genomics,...

Background: Emerging research suggests that increasing physical activity can help improve cognition among breast cancer survivors. However, little is known about the mechanism through which physical activity impacts cancer survivors' cognition. Objective: The objective of this secondary analysis examined physical and psychological function poten...

Background The association between sugar-sweetened beverage (SSB) consumption and colorectal cancer (CRC) risk remains unclear and published data are limited. Methods The analytic cohort included 99,798 women, free of cancer at baseline, from the California Teachers Study, a longitudinal cohort comprised of 133,477 female teachers and administrato...

Background and Hypothesis: Extracellular vesicles (EVs) are membrane-bound particles shed from a variety of cell types. They contain molecular cargo from the parent cell including metabolites, proteins, and nucleic acids. EVs are present in biofluids and could be promising biomarkers for monitoring wellness. Total sedentary time is linearly associa...

Purpose Cancer survivors are highly sedentary and have low physical activity. How physical activity interventions impact sedentary behavior remains unclear. This secondary analysis examined changes in sedentary behavior among breast cancer survivors participating in a physical activity intervention that significantly increased moderate-to-vigorous...

Background: Persons with schizophrenia and schizoaffective disorder (PwS) have high rates of cardiometabolic pathology that contributes to premature mortality. Adiponectin is a metabolic hormone affecting insulin sensitivity and inflammation, and is active in the brain. High-molecular weight (HMW) adiponectin is considered a more sensitive marker...

Background: The prevalence of obesity and the metabolic syndrome (MetS) has increased dramatically in developed countries over the last three decades (Flegal et al., 2012). Numerous studies indicate that adiposity and the MetS are independent risk factors for multiple diseases including cancer, particularly postmenopausal breast cancer (Kim et al.,...

To understand the health impact of long-duration spaceflight, one identical twin astronaut was monitored before, during, and after a 1-year mission onboard the International Space Station; his twin served as a genetically matched ground control. Longitudinal assessments identified spaceflight-specific changes, including decreased body mass, telomer...