Paul Martin CoenAdventHealth Orlando · Translational Research Institute
Paul Martin Coen
PhD
About
207
Publications
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Introduction
Dr. Paul Coen is an Associate Investigator at the Translational Research Institute for Metabolism and Diabetes, AdventHealth Orlando.Paul’s research program is supported by the National Institutes of Health (NIH) and is broadly focused on elucidating the role of skeletal muscle mitochondrial energetics in the pathophysiology’s associated with aging and obesity.
Additional affiliations
September 2013 - present
Florida Hospital, Translational Research Institute for Metabolism and Diabetes
Position
- Investigator
September 2013 - present
Sanford-Burnham-Prebys Medical Discovery Institute
Position
- Research Assistant
September 2013 - June 2017
Education
September 2003 - March 2008
September 2000 - August 2003
September 1996 - May 2000
Publications
Publications (207)
We tested the primary hypotheses that sphingolipid and diacylglycerol (DAG) content is higher within insulin-resistant muscle and that the association between intramyocellular triglycerides (IMTG) and insulin resistance is muscle fiber type specific.
A nested case-control analysis was conducted in 22 obese (BMI >30 kg/m(2)) women who were classifie...
Background:
Roux-en-Y gastric bypass (RYGB) surgery causes profound weight loss and improves insulin sensitivity (S(I)) in obese patients. Regular exercise can also improve S(I) in obese individuals; however, it is unknown whether exercise and RYGB surgery-induced weight loss would additively improve S(I) and other cardiometabolic factors.
Method...
Both Roux-en-Y gastric bypass (RYGB) surgery and exercise can improve insulin sensitivity (SI) in individuals with severe obesity. However, the impact of RYGB with or without exercise on skeletal muscle mitochondria, intramyocellular lipids and SI is unknown. We conducted a randomized exercise trial in patients (N=101) who underwent RYGB surgery an...
Background: Brown adipose tissue (BAT) is an important tissue for thermogenesis, making it a potential target to decrease the risks of obesity, type 2 diabetes, and cardiovascular disease (CVD), and recent studies have also identified BAT as an endocrine organ. While BAT has been implicated to be protective in cardiovascular disease, to this point...
Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that...
Greater perceived physical fatigability and lower skeletal muscle energetics are both predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of in vivo (maximal ATP production, ATPmax) and ex viv...
Objectives
Non-Hispanic black women (BW) have a greater risk of type 2 diabetes (T2D) and insulin resistance (IR) compared to non-Hispanic white women (WW). The mechanisms leading to these differences are not understood, and it is unclear whether synergistic effects of race and obesity impact disease risk. To understand the interaction of race and...
Background
Fatigability in community-dwelling older adults is highly prevalent and disabling, but lacks a treatment. Greater nigrostriatal dopaminergic signaling can ameliorate performance fatigability in healthy young adults, but its role in community-dwelling older adults is not known. We hypothesized that higher nigrostriatal dopaminergic integr...
Objective
Our objective was to investigate the overall and sex‐specific relationships between the presence and severity of knee osteoarthritis (KOA) and muscle composition, power, and energetics in older adults.
Methods
Male and female patients (n = 655, mean ± SD age 76.1 ± 4.9 years; 57% female) enrolled in the Study of Muscle, Mobility, and Agi...
Background
Slower gait speed may be driven by greater energy deficits and fatigability among older adults. We examined associations of walking energetics and perceived physical fatigability with gait speed among slower and faster walkers. Additionally, we used statistical mediation to examine the role of fatigability in the associations of walking...
With aging skeletal muscle fibers undergo repeating cycles of denervation and reinnervation. In approximately the 8th decade of life reinnervation no longer keeps pace, resulting in the accumulation of persistently denervated muscle fibers that in turn cause an acceleration of muscle dysfunction. The significance of denervation in important clinica...
Gene expression in skeletal muscle of older individuals may reflect compensatory adaptations in response to oxidative damage that preserve tissue integrity and maintain function. Identifying associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals...
Objective
The aim of this study was to examine associations of ectopic adipose tissue (AT) with skeletal muscle (SM) mitochondrial bioenergetics in older adults.
Methods
Cross‐sectional data from 829 adults ≥70 years of age were used. Abdominal, subcutaneous, and visceral AT and thigh muscle fat infiltration (MFI) were quantified by magnetic reson...
Greater perceived physical fatigability and lower skeletal muscle energetics are predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of in vivo (maximal ATP production, ATPmax) and ex vivo (ma...
Endurance exercise training is known to reduce risk for a range of complex diseases. However, the molecular basis of this effect has been challenging to study and largely restricted to analyses of either few or easily biopsied tissues. Extensive transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular...
Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood 1–3 . Here, the Molecular Transducers of Physical Activity Consortium ⁴ profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome...
Autophagy is essential for proteostasis, energetic balance, and cell defense and is a key pathway in aging. Identifying associations between autophagy gene expression patterns in skeletal muscle and physical performance outcomes would further our knowledge of mechanisms related with proteostasis and healthy aging. Muscle biopsies were obtained from...
Background
The geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity.
M...
Cardiorespiratory fitness and mitochondrial oxidative capacity are associated with reduced walking speed in older adults, but their impact on walking speed in older adults with diabetes has not been clearly defined. We examined differences in cardiorespiratory fitness and skeletal muscle mitochondrial oxidative capacity between older adults with an...
Social stress experienced in childhood is associated with adverse health later in life. Mitochondrial function has been implicated as a mechanism for how stressful life events “get under the skin” to influence physical well-being. Using data from the Study of Muscle, Mobility, and Aging ( n = 879, 59% women), linear models examined whether adverse...
Findings from the Study of Muscle, Mobility and Aging (SOMMA) in this issue of Aging Cell show that several biological pathways in skeletal muscle cells play an important role in determining mobility in older adults. These are based on assays in skeletal muscle biopsies obtained from participants, aged 70 years and older in SOMMA tested for associa...
Background:
The effects of aging on circadian patterns of behavior are insufficiently described. To address this, we characterized age-specific features of rest-activity rhythms (RAR) in community dwelling older adults both overall, and in relation, to sociodemographic characteristics.
Methods:
We examined cross-sectional associations between RA...
Background
How magnetic resonance (MR) derived thigh muscle volume and d3-creatine dilution derived muscle mass (D3Cr muscle mass) differentially relate to strength, fitness, and other functional in older adults - and whether associations vary by sex - is not known.
Methods
Men (N=345) and women (N=482) aged ≥70 years from the Study of Muscle, Mob...
Background
Muscle mass loss may be associated with liver fat accumulation, yet scientific consensus is lacking and evidence in older adults is scant. It is unclear which muscle characteristics might contribute to this association in older adults.
Methods
We associated comprehensive muscle-related phenotypes including muscle mass normalized to body...
Oxidative stress is considered a contributor to declining muscle function and mobility during aging; however, the underlying molecular mechanisms remain poorly described. We hypothesized that greater levels of cysteine (Cys) oxidation on muscle proteins are associated with decreased measures of mobility. Herein, we applied a novel redox proteomics...
Background
Skeletal muscle energetics decline with age, and physical activity (PA) has been shown to offset these declines in older adults. Yet, many studies reporting these effects were based on self-reported PA or structured exercise interventions. Therefore, we examined the associations of accelerometry-measured and self-reported PA and sedentar...
Exercise mediates tissue metabolic function through direct and indirect adaptations to acylcarnitine (AC) metabolism, but the exact mechanisms are unclear. We found that circulating medium-chain acylcarnitines (AC) (C12-C16) are lower in active/endurance trained human subjects compared to sedentary controls, and this is correlated with elevated car...
Background:
Walking slows with aging often leading to mobility disability. Mitochondrial energetics has been found to be associated with gait speed over short distances. Additionally, walking is a complex activity but few clinical factors that may be associated with walk time have been studied.
Methods:
We examined 879 participants ≥70 years and...
Background
Falls in the older population are a major public health concern. While many physiological and environmental factors have been associated with fall risk, muscle mitochondrial energetics has not yet been investigated.
Methods
In this analysis, 835 Study of Muscle, Mobility and Aging (SOMMA) participants aged 70-94 were surveyed for number...
The age-related decline in muscle mitochondrial energetics contributes to the loss of mobility in older adults. Women experience a higher prevalence of mobility impairment compared to men, but it is unknown whether sex-specific differences in muscle energetics underlie this disparity. In the Study of Muscle, Mobility and Aging (SOMMA), muscle energ...
Background
Cardiopulmonary exercise testing (CPET), the gold‐standard method to quantify cardiorespiratory fitness (CRF), is not always feasible due to cost, access, and burden. The usual‐paced 400 m long distance corridor walk (LDCW), a measure of mobility among older adults, may provide an alternate method to assess CRF. The purpose of this study...
Lower cardiorespiratory fitness among older adults is associated with greater multimorbidity burden, including cardiovascular disease, cancer, and dementia. Those with poorer muscle mitochondrial energetics also have lower cardiorespiratory fitness. We have previously shown lower mitochondrial respiration and energetics (OXPHOS and ATPmax) have hig...
We investigated the association of diabetes with cardiorespiratory fitness and skeletal muscle mitochondrial energetics in older adults (N=876, mean age ± SD: 76.3 ± 5.0 yrs.; 59% females) from the Study of Muscle, Mobility and Aging (SOMMA). Participants were grouped by self-reported diabetes status (N=131, with diabetes). Cardiorespiratory fitnes...
Aging leads to a decline in mitochondrial energetics of skeletal muscle. We hypothesize that worse mitochondrial energetics is associated with greater comorbidity burden and worse fatiguability. Furthermore, sex differences in mitochondrial decline with aging are poorly understood. Prior human muscle biopsy studies have tended to be small and did n...
Phenotypic frailty syndrome identifies older adults at greater risk for adverse health outcomes. Despite the critical role of mitochondria in maintaining cellular function, including energy production, the associations between muscle mitochondrial energetics and frailty have not been widely explored in a large, well-phenotyped, older population.
Th...
Background: Aging is associated with declines in circadian functions. The effects of aging on circadian patterns of behavior are insufficiently described. We characterized age-specific features of rest-activity rhythms (RAR) in community dwelling older adults, both overall, and in relation, to sociodemographic characteristics.
Methods: We analyzed...
Background: Different measures to assess muscle size - magnetic resonance (MR) derived thigh muscle volume and d3-creatine dilution derived muscle mass (D3Cr muscle mass) - may have similar associations with strength, power, physical performance, fitness, and functional limitations in older adults.
Methods: Men (N=345) and women (N=482) aged ≥70 ye...
Background: Walking slows with aging often leading to mobility disability. Mitochondrial energetics has been found to influence gait speed over short distances. Additionally, walking is a complex activity but few clinical factors that may influence walk time have been studied.
Methods: We examined 879 participants ≥70 years and measured the time to...
Objective: Examine the association of ectopic adipose tissue (AT) with skeletal muscle (SM) mitochondrial bioenergetics in older adults.
Methods: Cross-sectional data from 829 older adults ≥70 years was used. Total abdominal, subcutaneous, and visceral AT; and thigh muscle fat infiltration (MFI) was quantified by MRI. SM mitochondrial energetics we...
The age-related decline in muscle mitochondrial energetics contributes to the loss of mobility in older adults. Women experience a higher prevalence of mobility impairment compared to men, but it is unknown whether sex-specific differences in muscle energetics underlie this disparity. In the Study of Muscle, Mobility and Aging (SOMMA), muscle energ...
Background: Falls in the older population are a major public health concern. While many physiological and environmental factors have been associated with fall risk, muscle mitochondrial energetics has not yet been investigated.
Methods: In this analysis, 835 Study of Muscle, Mobility and Aging (SOMMA) participants aged 70-94 were surveyed for recur...
Social stress experienced in childhood is associated with adverse health later in life. Mitochondrial function has been implicated as a mechanism for how stressful life events get under the skin to influence physical wellbeing. Using data from the Study of Muscle, Mobility and Aging (n=879, 59% women), linear models examined whether adverse childho...
Oxidative stress is considered a contributor to declining muscle function and mobility during aging; however, the underlying molecular mechanisms remain poorly described. We hypothesized that greater levels of cysteine (Cys) oxidation on muscle proteins are associated with decreased measures of mobility. Herein, we applied a novel redox proteomics...
Background. The geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity.
M...
Gene expression in skeletal muscle of older individuals may reflect compensatory adaptations in response to oxidative damage that preserve tissue integrity and maintain function. Identifying associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals...
Background: Cardiopulmonary exercise testing (CPET), the gold-standard method to quantify cardiorespiratory fitness (CRF), is not always feasible due to cost, access, and burden. The usual-paced 400m long-distance corridor walk (LDCW), a measure of mobility among older adults, may provide an alternate method to assess CRF among populations unable t...
Background: Slow gait speed is a risk factor for poor health outcomes among older adults and may be driven by decreased energy availability and increased fatigability.
Objective: Examine walking energetics and perceived physical fatigability with gait speed among slower and faster walkers and understand whether fatigability statistically mediates t...
Background: Skeletal muscle energetics decline with age, and physical activity (PA) has been shown to counteract these declines in older adults. Yet, many studies were based on self-reported PA or structured exercise interventions. We examined the associations of objective daily PA and sedentary behavior (SB) with skeletal muscle energetics and als...
With aging skeletal muscle fibers undergo repeating cycles of denervation and reinnervation. In approximately the 8th decade of life reinnervation no longer keeps pace, resulting in the accumulation of persistently denervated muscle fibers that in turn cause an acceleration of muscle dysfunction. The significance of denervation in important clinica...
Autophagy is an essential component of proteostasis and a key pathway in aging. Identifying associations between autophagy gene expression patterns in skeletal muscle and physical performance outcomes would further our knowledge of mechanisms related with proteostasis and healthy aging. Muscle biopsies were obtained from participants in the Study o...
Rationale: Cardiorespiratory fitness and mitochondrial energetics are associated with reduced walking speed in older adults. The impact of cardiorespiratory fitness and mitochondrial energetics on walking speed in older adults with diabetes has not been clearly defined.
Objective: To examine differences in cardiorespiratory fitness and skeletal mus...
Background
Muscle mass loss may be associated with liver fat accumulation, yet scientific consensus is lacking and evidence in older adults is scant. It is unclear which muscle characteristics might contribute to this association in older adults.
Methods
We associated comprehensive muscle-related phenotypes including muscle mass normalized to body...
Background:
Frailty can occur in older adults without disability or multimorbidity. Current methods focus on the most frail, but poorly discriminate among those "not frail".
Methods:
The Study of Muscle, Mobility and Aging (SOMMA) included 879 adults aged 70 years and older without mobility disability. We operationalized frailty domains using: p...
Performance fatigability is typically experienced as insufficient energy to complete daily physical tasks, particularly with advancing age, often progressing toward dependency. Thus, understanding the etiology of performance fatigability, especially cellular‐level biological mechanisms, may help to delay the onset of mobility disability. We hypothe...
Microphysiological systems provide the opportunity to model accelerated changes at the human tissue level in the extreme space environment. Spaceflight-induced muscle atrophy experienced by astronauts shares similar physiological changes to muscle wasting in older adults, known as sarcopenia. These shared attributes provide a rationale for investig...
Objective:
The prevalence of type 2 diabetes in African American women (AAW) is nearly twice that of White women. Lower insulin sensitivity and decreased mitochondrial function may be contributing factors. The purpose of this study was to compare fat oxidation in AAW and White women.
Methods:
Participants were 22 AAW and 22 White women, matched...
Exercise‐induced perturbation of skeletal muscle metabolites is a probable mediator of long‐term health benefits in older adults. Although specific metabolites have been identified to be impacted by age, physical activity and exercise, the depth of coverage of the muscle metabolome is still limited. Here, we investigated resting and exercise‐induce...
Metabolic routing of nicotinamide (NAM) to NAD+ or 1-methylnicotinamide (MeNAM) has impacts on human health and aging. NAM is imported by cells or liberated from NAD+. The fate of 2H4-NAM in cultured cells, mice, and humans was determined by stable isotope tracing. 2H4-NAM is an NAD+ precursor via the salvage pathway in cultured A549 cells and huma...
Microgravity-induced muscle atrophy experienced by astronauts shares similar physiological changes to muscle wasting experienced by older adults, known as sarcopenia. These shared attributes provide a rationale for investigating microgravity-induced molecular changes in human bioengineered muscle cells that may also mimic the progressive underlying...
Background:
The Study of Muscle, Mobility and Aging (SOMMA) aims to understand the biological basis of many facets of human aging, with a focus on mobility decline, by creating a unique platform of data, tissues, and images.
Methods:
The multidisciplinary SOMMA team includes two clinical centers (University of Pittsburgh and Wake Forest Universi...
Mitochondria are adaptable organelles with diverse cellular functions critical to whole-body metabolic homeostasis. While chronic endurance exercise training is known to alter mitochondrial activity, these adaptations have not yet been systematically characterized. Here, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) mapped the...
Muscle fitness and mass deteriorate under the conditions of obesity and aging for reasons yet to be fully elucidated. Herein, we describe a novel pathway linking peripheral nutrient sensing and skeletal muscle function through the sweet taste receptor TAS1R2 and the involvement of ERK2-PARP1-NAD signaling axis. Muscle-specific deletion of TAS1R2 (m...
We used canonical correlation (n=424) to examine the relationships between a set of physical function measures (400m usual pace, chair stands/sec, 4m walk pace, standing balance times, VO2 peak, muscle power, four-square step test (FSST) time, stair climb time and stair climb power) and a set of cognitive measures (Trail Making Test B (sec), Digit...
Peak aerobic capacity declines with age concomitant with greater fatigability and slower gait speed. We explored these relationships with cross-sectional SOMMA data (N=422, age=76.7±5.1, 57.4% women, gait speed= 0.97±0.18 m/s from a 4m walk). Participants completed a treadmill peak oxygen consumption test (VO2peak) and the self-administered Pittsbu...
Longer 400m walking time has been strongly associated with overall mortality and many other aging-related outcomes in prior studies. Inability to walk 400m defines ‘mobility disability’. We assessed characteristics that might contribute to 400m walking time in SOMMA, a cohort of 879 men and women over age 70. We excluded people with a gait speed <...
We studied whether lower physical activity (PA) in older adults may partly explain the age-related decline in muscle mitochondrial function in the SOMMA cohort of 879 men and women, aged 70+. PA was measured both subjectively (CHAMPS questionnaire) and objectively (wrist-worn ActiGraph Link) classifying PA levels as sedentary, light, or moderate to...
We screened approximately 4200 individuals to enroll 881 including 41% men and 59% women with a mean age =73.4 ± 5SD years; 13% were Black, 85% White and 2% of other race and ethnic groups. We will add 80 individuals aged 30-69 years. Exclusions included unstable medical conditions and inability to walk 400 meters(m). The median baseline 400m gait...
To assess mitochondrial function, max OXPHOS (maximal complex I and II supported state 3 respiration) was determined in vitro by high-resolution respirometry of permeabilized muscle fibers from thigh muscle (vastus lateralis) biopsies, and ATPmax was determined in vivo by 31P magnetic resonance spectroscopy (n=468, mean=76.9yr). Max OXPHOS was stro...
SOMMA aims to characterize key muscle characteristics and their longitudinal association with declines in mobility. To assess mitochondrial energetics in muscle, respiration assays were performed on biopsies of the vastus lateralis and the capacity to generate ATP (ATPmax) was determined by 31P MR spectroscopy. Other properties examined in biopsies...
Mobility impairment is the most common disability among older adults, with an earlier presentation, higher prevalence, and greater severity in women compared to men. A decline in skeletal muscle metabolism contributes to the loss of mobility with age. However, it is unknown if sex-specific differences in muscle energetics can explain the disparity...
D3Cr muscle mass, grip strength, leg extension 1-rm max (Keiser), and walking speed (400m usual walk) were collected with standardized protocols. We calculated sex-stratified unadjusted Pearson correlation coefficients, and partial Pearson correlation coefficient adjusted for body size (height, weight). D3Cr muscle mass was positively correlated wi...
Background:
Mitochondrial energetics are an important property of aging muscle, as generation of energy is pivotal to the execution of muscle contraction. However, its association with functional outcomes, including leg power and cardiorespiratory fitness is largely understudied.
Methods:
In the Study of Muscle, Mobility, and Aging (SOMMA), we c...
Regular exercise promotes whole-body health and prevents disease, yet the underlying molecular mechanisms throughout a whole organism are incompletely understood. Here, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylpr...