Jeremy Walston

Jeremy Walston
Johns Hopkins University | JHU · Department of Medicine

MD

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346
Publications
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Introduction
Skills and Expertise

Publications

Publications (346)
Article
Chronic inflammation, oxidative stress, and dysregulation of the renin-angiotensin system are closely linked, and their crosstalk commonly contributes to age-related physical and cognitive decline. The primary dementia-protective benefits of Angiotensin II receptor type 1 (AT1R) blockers are believed to arise from systemic effects on blood pressure...
Article
Objectives: Our primary objective was to examine the distribution of 3-m usual walk, five repeated chair stands, and three static balance stance performances among age and gender subgroups of adults at least 65 years in two national data sets. We secondarily determined whether demographic-function associations varied across data sets, birth cohort...
Article
Background: Alzheimer's disease (AD) is the most common cause of dementia. Although multiple potential etiologies have been proposed, no clear aging-related etiological mechanisms have been identified. Renin Angiotensin system (RAS) is a hormonal system that is implicated in blood pressure control and has been suggested as a potential contributor...
Article
Background Self-reported low physical activity is a defining feature of phenotypic frailty but does not adequately capture physical activity performed throughout the day. This study examined associations between accelerometer-derived patterns of routine daily physical activity and frailty. Methods Wrist accelerometer and frailty data from 638 part...
Article
Background Total knee replacement (TKR) is a common procedure in older adults. Physical resilience may be a useful construct to explain variable outcomes. We sought to define a simple measure of physical resilience and identify risk factors for non-resilient patient outcomes. Methods Secondary analysis of FORCE-TJR cohort study, a prospective regi...
Article
Background: Chronic inflammation (CI) is a common trait of aging associated with adverse outcomes including mortality. We hypothesized that recombinant human Lactoferrin (rhLf) would reduce chronic inflammation of aging. Methods: Thirty-six community dwelling older adults were randomly assigned to rhLf or placebo treatment in 1:1 ratio for 3 mon...
Article
Full-text available
The cellular hallmarks of accelerated aging and their clinical expression may be grouped using the terms ‘accelerated aging and cellular decline’ (AACD) and/or ‘age-associated cellular decline’. This construct is designed to capture the biological background predisposing the development of age-related conditions. By classifying risk factors, early...
Article
Full-text available
Ageing in humans is associated with the decreased capacity to regulate cell physiology. Cellular properties, such as cell morphology and mechanics, encode ageing information, and can therefore be used as robust biomarkers of ageing. Using a panel of dermal fibroblasts derived from healthy donors spanning a wide age range, we observe an age-associat...
Article
Frailty in aging marks a state of decreased reserves resulting in increased vulnerability to adverse outcomes when exposed to stressors. This Perspective synthesizes the evidence on the aging-related pathophysiology underpinning the clinical presentation of physical frailty as a phenotype of a clinical syndrome that is distinct from the cumulative-...
Article
Full-text available
Frailty is triggered by inflammatory pathways among patients with end-stage kidney disease (ESKD). Exposure to air pollution is associated with increased inflammation and as such may be a determinant of frailty in patients with ESKD. Therefore, we sought to estimate the impact of household-level exposure to fine particulate matter (particles <2.5μm...
Article
Full-text available
Seven million adults in the United States are homebound and suffer the negative, powerful synergies of multiple chronic conditions, functional impairment, social stressors, and limited social capital. The prevalence of frailty in this vulnerable homebound population is unknown. Using representative data from the National Health and Aging Trends stu...
Article
Full-text available
This talk presents the conceptual framework, study design, and pilot data for the Study of Physical Resilience and agING (SPRING). SPRING aims to develop signatures of physical resilience in older adults who will undergo clinical stressors; validate the signatures’ ability to distinguish those who will respond resiliently; and characterize underlyi...
Article
Full-text available
Total knee replacement (TKR) is a common procedure in older adults with broad variability in outcomes. We sought to identify factors that contribute to resilient outcomes in 7,239 older adults (age 60 or older) who underwent TKR in the TJR-FORCE, a prospective registry of total joint replacement. Outcomes utilized were bodily pain and physical comp...
Article
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Blood samples were collected from participants in the REGARDS study on two separate occasions. No participants in the Caregiving Transitions Study were caregivers at the first blood draw, but 251 became caregivers before the second blood draw 9 years later. These caregivers were matched with 251 noncaregiving controls. Six circulating biomarkers of...
Article
Full-text available
Physical frailty is defined as a syndrome of decreased physiologic reserve conferring vulnerability to functional decline, mortality and other adverse outcomes in response to a stressor. One potential modifiable risk factor of frailty is self-efficacy, which is confidence in one’s ability to perform well at a task or domain in life. Self-efficacy i...
Article
Full-text available
The Resiliency in Dialysis Initiation (ReDI) Study aims to develop physical resilience signatures in older adults initiating hemodialysis. Study design—comprising a pilot, confirmatory study, and secondary data analyses—will be presented. So also will a method for characterizing resilience phenotypes—using mixed-model analysis of SF-36 subscale tra...
Article
Mitochondrial dysfunction and subsequently impaired energetics triggering cell death have been observed in both dementia and frailty. Cell death releases circulating cell‐free DNA (ccf‐DNA) from mitochondrial (ccf‐mtDNA) and nuclear (ccf‐nDNA) sources. Size and relative abundance of ccf‐mtDNA fragments is suggestive of mechanism of cell death; long...
Article
Full-text available
Background: Physical frailty in older individuals is characterized by subjective symptoms of fatigue and exercise intolerance (EI). Objective abnormalities in skeletal muscle (SM) mitochondrial high-energy phosphate (HEP) metabolism contribute to EI in inherited myopathies, but their presence or link to EI in the frail older adult is unknown. Met...
Article
Older adults are far more vulnerable to adverse health outcomes and mortality after contracting COVID-19. There are likely multiple age-related biological, clinical and environmental reasons for this increased risk, all of which are exacerbated by underlying age-associated changes to the immune system as well as increased prevalence of chronic dise...
Article
Full-text available
Chronic inflammation is associated with physical frailty and functional decline in older adults; however, the molecular mechanisms of this linkage are not understood. A mouse model of chronic inflammation showed reduced motor function and partial denervation at the neuromuscular junction. Metabolomic profiling of these mice and further validation i...
Article
Background Physical frailty phenotype (PFP) is characterized by decreased physiologic reserve to stressors and associated with poor outcomes, such as delirium and mortality, that may result from post-kidney transplant (KT) inflammation. Despite a hypothesized underlying pro-inflammatory state, conventional measures of frailty typically do not incor...
Article
Background: Although frailty has been associated with major morbidity/mortality and increased length of stay after cardiac surgery, few studies have examined functional outcomes. We hypothesized that frailty would be independently associated with decreased functional status, increased discharge to a nonhome location, and longer duration of hospita...
Article
Introduction Multifactorial biological processes underpin dysregulation over several individual physiological systems. However, it is challenging to characterize and model this multisystemic dysregulation and its relationship with individual physiologic systems. We operationalized a theory-driven measure of multisystem dysregulation and empirically...
Preprint
Ageing in humans is associated with a decreased capacity to regulate cell physiology. Cellular properties, such as cell morphology and cell mechanics, encode ageing information and as a result can be used as robust ageing biomarkers. Using a panel of dermal fibroblasts derived from healthy donors spanning a wide age range, we observe an age-related...
Article
Background Skeletal muscle wasting, or sarcopenia, affects a significant proportion of patients undergoing TAVR. However, its influence on post-TAVR recovery and one-year health-related quality of life (HR-QOL) remains unknown. We examined the relationship between skeletal muscle index (SMI), post TAVR length of hospital stay (LOS), and one-year QO...
Article
Full-text available
The connection between aging-related immune dysfunction and the lung manifestations of aging is poorly understood. A detailed characterization of the aging IL10-deficient murine lung, a model of accelerated aging and frailty, reconciles features of both immunosenescence and lung aging in a coherent model. Airspace enlargement developed in the middl...
Article
Full-text available
Chronic inflammation is associated with frailty and functional decline in older adults but the molecular mechanisms of this linkage are not well understood. We sought to examine metabolic and physiologic states associated with aging and frailty by analyzing the composition of metabolites in the blood of a population of community dwelling young, and...
Article
Full-text available
Cardiovascular disease (CVD) and frailty have been linked at the mechanistic and epidemiological levels. Our goal is to identify if subclinical markers such as atherosclerosis, body composition, and fibrofatty infiltration measured from non-contrast whole-body magnetic resonance imaging (MRI) are markers of physical frailty. Community dwelling olde...
Article
Background/aim Cost-efficient methods are essential for successful participant recruitment in clinical trials. Patient portal messages are an emerging means of recruiting potentially eligible patients into trials. We assessed the response rate and complaint rate from direct-to-patient, targeted recruitment through patient portals of an electronic m...
Article
This letter comments on the letter by Strandberg et al.
Article
Full-text available
Objectives: Frailty affects an estimated 15% of community dwelling older adults. Few studies look at psychosocial variables like self-efficacy (confidence to perform well at a particular task or life domain) in relation to frailty. The purpose of this study was to evaluate associations between pre-frailty/frailty and self-efficacy. Methods: This cr...
Article
Frailty has long been an important concept in the practice of geriatric medicine and in gerontological research, but integration and implementation of frailty concepts into clinical practice in the United States has been slow. The National Institute on Aging (NIA) Intramural Research Program and the Johns Hopkins Older Americans Independence Center...
Article
Background: Frailty is a geriatric syndrome thought to identify the most vulnerable older adults, and morbidity and mortality has been reported to be higher for frail patients after cardiac surgery compared to nonfrail patients. However, the cognitive consequences of frailty after cardiac surgery have not been well described. In this study, we exa...
Article
Background Although frailty status greatly impacts health care in countries with rapidly aging populations, little is known about the frailty status in Chinese older adults. Objectives Given the increased health care needs associated with frailty, we sought to develop an easily applied self-report screening tool based on four of the syndromic fr...
Article
Frailty is a syndrome of accelerated aging-related multisystemic decline that affects a subset of the most vulnerable older adults. While changes in metabolism have been implicated in development of frailty, comprehensive analyses of metabolic products that differentiate frail from resilient individuals and correlate with physical decline have not...
Article
In older adults, cellular senescence is linked to frailty and risk of death. Senescent cells accumulate dysfunctional mitochondria. With cell turnover, mtDNA fragments are released into circulation. These fragments can be utilized as biomarker for cell turnover and to distinguish apoptotic vs necrotic cell death. The utility of circulating-cell-fre...
Conference Paper
Background/Objective: Frailty is an important predictive factor of adverse outcomes in older adults. Most of the frailty assessment tools are time-consuming or require objective measurements, therefore, difficult to implement in routine clinical work. The best-known tool is the frailty phenotype derived from a hypothesis that frailty has a deeply b...
Conference Paper
Backgrounds: Despite many conceptualizations of frailty have been proposed, the most frequently used measure is the frailty phenotype which describes frailty as a clinical syndrome of low physical activity, slowness, weakness, weight loss, and fatigue. It will not be applied in primary care or clinic settings without a standardized measurement. Alt...
Article
Prior evidence suggests that vitamin D supplementation may reduce fall risk, but existing data are inconsistent and insufficient to guide policy. We designed a two-stage Bayesian response-adaptive dose-finding and seamless confirmatory randomized trial of vitamin D supplementation to prevent falls. Up to 1200 community-dwelling persons, aged ≥70 ye...
Conference Paper
Background: Although frailty status greatly impacts health care in countries with rapidly aging populations, little is known about the frailty status in Chinese older adults. Given the increased health care needs associated with frailty, we sought to develop an easily applied self-report screening tool based on four of the syndromic frailty compone...
Conference Paper
Background: In older adults chronic inflammation (CI) commonly accompanies frailty and increases risk of mortality. From all the different pro-inflammatory cytokines that were demonstrated to be increased in frailty, IL-6 elevation was independently associated with worse decline and with the progression of age related diseases. IL-6 has been theref...
Conference Paper
Background: Decline in mitochondrial function is a primary theory of aging. With aging, higher levels of free radical are generated and are associated with increased mitochondrial DNA mutations and mitochondrial death. With cell death, fragments of mitochondrial DNA are released into the circulation. Based on the size, mitochondrial fragment can be...
Article
Background: Among community-dwelling older adults, frailty is associated with heightened markers of inflammation and subsequent mortality. Although frailty is common among ESRD patients, the role of frailty and markers of inflammation in this population remains unclear. We quantified these associations in patients on the kidney transplant (KT) wai...
Conference Paper
Background: Chronic inflammation (CI) is strongly associated with functional decline, chronic disease states, reduced health span, and mortality in mouse models and humans. Interleukin 6 (IL-6) is one of the markers of CI that is strongly and consistently associated with age-related adverse health outcomes, however, the specific role of IL-6 has no...
Article
Frailty is recognized as a cornerstone of geriatric medicine. It increases the risk of geriatric syndromes and adverse health outcomes in older and vulnerable populations. Although multiple screening instruments have been developed and validated to improve feasibility in clinical practice, frequent lack of agreement between frailty instruments has...
Article
Full-text available
Interleukin 10tm1Cgn (IL 10tm) mice have been utilized as a model of chronic inflammation and declining health span because of their propensity to develop chronic activation in NFkB pathways, skeletal muscle and cardiac changes, and mitochondrial dysfunction. We hypothesized that older IL 10tm frail mice would have alterations similar to frail, old...
Data
Oxygen consumption normalized by total body weight (top) and lean mass (bottom) in old aged IL 10tm (Panel A & Panel B). Each line connects the mean of each genotype (n = 10 per genotype). (TIF)
Data
Intra-peritoneal glucose tolerance test in young (Panel A), middle (Panel B) and old (Panel C) mice. (TIF)
Data
Metabolic panel. Plasma measurements of glucose (Panel A), and creatine kinase (Panel B). (TIF)
Data
Additional hematologic features of IL 10tm and control mice. (DOCX)
Data
Rearing (Z-Axis) activity measured during indirect calorimetry using an infrared beam grid & sensors. For young (Panel A), middle aged (Panel B), and old (Panel C). (TIF)
Data
Histogram of fat cell size in old IL 10tm (Panel A) and control mice (Panel B). (TIF)
Data
CD11b macrophage/ monocyte immunohistochemistry protocol. (DOCX)
Data
Oxygen consumption normalized by lean mass (top) and fat mass (bottom) in middle aged IL 10tm (Panel A & B), young aged (Panel C & D). Each animal’s range of 48 hour VO2 is depicted by a single vertical group of points with a line connecting the means of each animal across each genotype. (TIF)
Data
Respiratory quotient in old IL 10tm (Panel C), middle aged (Panel B) and young (Panel A). Lines connect means of each genotype (n = 10 per genotype). (TIF)
Data
Oral glucose tolerance test in young (Panel A), middle (Panel B) and old (Panel C) mice. (TIF)
Data
Comprehensive plot of body weights of both groups across all ages. (TIF)
Data
Change in body weight and food consumed per gram bodyweight during indirect calorimetry for all groups. (TIF)
Chapter
Frailty is an increasingly common condition of late life vulnerability that puts older adults at high risk for adverse health outcomes and early mortality. There are two major conceptualizations of frailty: the physical or frailty phenotype, which suggests that frailty is driven by deep biological changes in multiple physiological systems; and the...
Article
Chronic wounds are among the most devastating and difficult to treat consequences of diabetes. Dysregulation of the skin renin-angiotensin system (RAS) is implicated in abnormal wound healing in diabetic and older adults. Given this, we sought to determine the effects of topical reformulations of the angiotensin type 1 receptor blockers (ARB) losar...
Article
Objectives: To test two interventions to reduce interleukin (IL)-6 levels, an indicator of low-grade chronic inflammation and an independent risk factor for impaired mobility and slow walking speed in older adults. Design: The ENabling Reduction of low-Grade Inflammation in SEniors (ENRGISE) Pilot Study was a multicenter, double-blind, placebo-c...
Article
Full-text available
Ageing research has focused either on assessing organ- and tissue-based changes, such as lung capacity and cardiac function, or on changes at the molecular scale such as gene expression, epigenetic modifications and metabolism. Here, by using a cohort of 32 samples of primary dermal fibroblasts collected from individuals between 2 and 96 years of a...
Article
Although the field of frailty research has expanded rapidly, it is still a nascent concept within the clinical specialties. Frailty, conceptualized as greater vulnerability to stressors because of significant depletion of physiological reserves, predicts poorer outcomes in several medical specialties, including cardiology, human immunodeficiency vi...
Article
Full-text available
Background: Fried and colleagues described a frailty phenotype measured in the Cardiovascular Health Study (CHS). This phenotype is manifest when ≥3 of the following are present: low grip strength, low energy, slowed waking speed, low physical activity, or unintentional weight loss. We sought to approximate frailty phenotype using only administrat...
Article
Full-text available
OBJECTIVES: Evidence suggests vitamin D deficiency is associated with developing frailty. However, cardiometabolic factors are related to both conditions and may confound and/or mediate the vitamin D–frailty association. We aimed to determine the association of vitamin D concentration with incidence of frailty, and the role of cardiometabolic disea...
Article
Importance: In one-third of older men with anemia, no recognized cause can be found. Objective: To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration. Design, setting, and participants: A double-blinded, placebo-controlled...
Article
Chronic inflammation is associated with muscle weakness and frailty in older adults. The antagonistic cross-talk between macrophage migration inhibitory factor (Mif), an anti-apoptotic cytokine and NIP3-like protein X (Nix), a pro-apoptotic mitochondrial protein, may play a role in mitochondrial free radical homeostasis and inflammatory myopathies....
Article
Full-text available
Older patients with ESRD who receive a kidney transplant (KT) may develop post-KT dementia and Alzheimer's disease (AD) associated with their long-standing kidney disease and/or neurotoxic immunosuppressant agents. To investigate this possibility, we studied 40,918 older (aged ≥55 years) KT recipients (January 1, 1999 to December 31, 2011) linked t...