Institute of Aging Research

Boston, MA, United States

Institute of Aging Research

Boston, MA, United States
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Fortenbaugh F.C.,Translational Research Center for and Stress Disorders and Geriatric Research | Fortenbaugh F.C.,Neuroimaging Research for Veterans e Center | Fortenbaugh F.C.,Harvard University | Corbo V.,Translational Research Center for and Stress Disorders and Geriatric Research | And 19 more authors.
Brain and Behavior | Year: 2017

Introduction: Interpersonal early life trauma (I-ELT) is associated with a myriad of functional impairments in adulthood, increased risk of drug addiction, and neuropsychiatric disorders. While deficits in emotional regulation and amygdala functioning are well characterized, deficits in general cognitive functioning have also been documented. However, the neural underpinnings of cognitive dysfunction in adults with a history of I-ELT and the potential relationship between amygdala-based functional connectivity and behavioral performance are currently poorly understood. This study examined how I-ELT affects the cognitive and neural mechanisms supporting sustained attention. Methods: A total of 66 Veterans (18 with and 48 without a history of I-ELT) completed a nonemotional sustained attention task during functional MRI. Results: The individuals with I-ELT showed significant impairments in sustained attention (i.e., higher error rates, greater response variability). This cohort exhibited increased amygdala functional connectivity with the prefrontal cortex and decreased functional connectivity with the parahippocampal gyrus when compared to those without I-ELT. These connections were significantly correlated with individual differences in sustained attention performance. Notably, classification analyses revealed that the pattern of amygdala connectivity across the whole brain was able to classify I-ELT status with 70% accuracy. Conclusion: These results provide evidence of a lasting negative impact for those with a history of I-ELT on sustained attention ability. They also highlight a critical role for amygdala functioning in cognitive control and sustained attention for those with a history of I-ELT, which may underlie the observed attention deficits in clinical assessments and cognitive tests involving both emotional and nonemotional stimuli. © 2017 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.


Oh E.S.,University of Baltimore | Li M.,University of Washington | Fafowora T.M.,University of Baltimore | Inouye S.K.,Institute of Aging Research | And 6 more authors.
International Journal of Geriatric Psychiatry | Year: 2015

Objective Systematically identify preoperative clinical risk factors for incident postoperative delirium in individuals undergoing hip fracture repair in order to guide clinicians in identifying high risk patients at admission. Methods This is a systematic review of prospective observational studies with estimation of association between preoperative risk factors and incident postoperative delirium in multivariate models. Electronic searches were conducted in PubMed, Embase, PsycINFO, CINAHL, Cochrane Library, Proquest Dissertations and Theses, and WorldCatDissertations. Hand searches were conducted in selected journals and their supplements. Results Search yielded 6380 titles and abstracts from electronic databases and 72 titles from hand searches, and 10 studies met inclusion criteria. The following risk factors were significant in bivariate models: cognitive impairment, age, gender, institutionalization, functional impairment, body mass index (BMI), albumin, comorbidities, American Society of Anesthesiologist classification, acute medical conditions, polypharmacy, and vision impairment. Among all of these risk factors, cognitive impairment most consistently remained statistically significant after adjusting for other risk factors in multivariate models, followed by BMI/albumin and multiple comorbidities. Conclusion In our systematic review, cognitive impairment was one of the strongest preoperative risk factors for postoperative delirium after hip fracture surgery. Preoperative cognitive assessment may be one of the most useful methods of identifying those who are at high risk for postoperative delirium and prioritizing delivery of delirium prevention measures. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.


Hurria A.,Medical Oncology and Experimental TherapeuticsCity of Hope National Medical CenterDuarte | Cohen H.J.,Center for the Study of Aging and Human DevelopmentDuke UniversityDurham | Rowland J.H.,Office of Cancer SurvivorshipNational Cancer InstituteBethesda | Leach C.R.,Office of Cancer SurvivorshipNational Cancer InstituteBethesda | And 9 more authors.
Cancer | Year: 2016

In May 2015, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging through a U13 grant, convened a conference to identify research priorities to help design and implement intervention studies to improve the quality of life and survivorship of older, frailer adults with cancer. Conference attendees included researchers with multidisciplinary expertise and advocates. It was concluded that future intervention trials for older adults with cancer should: 1) rigorously test interventions to prevent the decline of or improve health status, especially interventions focused on optimizing physical performance, nutritional status, and cognition while undergoing cancer treatment; 2) use standardized care plans based on geriatric assessment findings to guide targeted interventions; and 3) incorporate the principles of geriatrics into survivorship care plans. Also highlighted was the need to integrate the expertise of interdisciplinary team members into geriatric oncology research, improve funding mechanisms to support geriatric oncology research, and disseminate high-impact results to the research and clinical community. In conjunction with the 2 prior U13 meetings, this conference provided the framework for future research to improve the evidence base for the clinical care of older adults with cancer. © 2016 American Cancer Society.


Wang Z.,Institute of Aging Research
Proteins: Structure, Function and Bioinformatics | Year: 2016

Malonyl-CoA decarboxylase (MCD) can control the level of malonyl-CoA in cell through the decarboxylation of malonyl-CoA to acetyl-CoA, and plays an essential role in regulating fatty acid metabolism, thus it is a potential target for drug discovery. However, the interactions of MCD with CoA derivatives are not well understood owing to unavailable crystal structure with a complete occupancy in the active site. To identify the active site of MCD, molecular docking and molecular dynamics simulations were performed to explore the interactions of human mitochondrial MCD (HmMCD) and CoA derivatives. The findings reveal that the active site of HmMCD indeed resides in the prominent groove which resembles that of CurA. However, the binding modes are slightly different from the one observed in CurA due to the occupancy of the side chain of Lys183 from the N-terminal helical domain instead of the adenine ring of CoA. The residues 300-305 play an essential role in maintaining the stability of complex mainly through hydrogen bond interactions with the pyrophosphate moiety of acetyl-CoA. Principle component analysis elucidates the conformational distribution and dominant concerted motions of HmMCD. MM_PBSA calculations present the crucial residues and the major driving force responsible for the binding of acetyl-CoA. These results provide useful information for understanding the interactions of HmMCD with CoA derivatives. © 2016 Wiley Periodicals, Inc.


Crandall J.P.,Diabetes Research and Training Center | Crandall J.P.,Institute of Aging Research | Trandafirescu G.,Diabetes Research and Training Center | Kishore P.,Diabetes Research and Training Center | And 6 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2012

Background. Resveratrol, a plant-derived polyphenol, has shown promising effects on insulin sensitivity and glucose tolerance in animal models and is also reported to have cardioprotective properties, but human studies are limited. In a pilot study, we tested the hypothesis that resveratrol improves glucose metabolism and vascular function in older adults with impaired glucose tolerance (IGT).Methods.Ten subjects aged 72 ± 3 years (M ± SD) with IGT were enrolled in a 4-week open-label study of resveratrol (daily dose 1, 1.5, or 2 g). Following a standard mixed meal (110 g carbohydrate, 20 g protein, 20 g fat), we measured 3-hour glucose and insulin area under the curve (AUC), insulin sensitivity (Matsuda index), and secretion (corrected insulin response at 30 minutes). Endothelial function was assessed by reactive hyperemia peripheral arterial tonometry (reactive hyperemia index) before and 90 minutes postmeal. Results did not differ by dose, so data were combined for analysis.Results.At baseline, body mass index was 29 ± 5 kg/m 2, fasting plasma glucose 110 ± 13 mg/dL, and 2-hour glucose 183 ± 33 mg/dL. After 4 weeks of resveratrol, fasting plasma glucose was unchanged, but peak postmeal (185 ± 10 vs 166 ± 9 mg/dL, p =. 003) and 3-hour glucose AUC (469 ± 23 vs 428 ± 19, p =. 001) declined. Matsuda index improved (3.1 ± 0.5 vs 3.8 ± 0.5, p =. 03), and corrected insulin response at 30 minutes was unchanged (0.6 ± 0.1 vs 0.5 ± 0.5, p =. 49). There was a trend toward improved postmeal reactive hyperemia index (baseline vs resveratrol postmeal delta -0.4 ± 0.2 vs 0.2 ± 0.3, p =. 06). Weight, blood pressure, and lipids were unchanged.Conclusions.At doses between 1 and 2 g/day, resveratrol improves insulin sensitivity and postmeal plasma glucose in subjects with IGT. These preliminary findings support the conduct of larger studies to further investigate the effects of resveratrol on metabolism and vascular function. © The Author 2012. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.


PubMed | University of Washington, Institute of Aging Research, Princeton University and University of Baltimore
Type: Journal Article | Journal: International journal of geriatric psychiatry | Year: 2015

Systematically identify preoperative clinical risk factors for incident postoperative delirium in individuals undergoing hip fracture repair in order to guide clinicians in identifying high risk patients at admission.This is a systematic review of prospective observational studies with estimation of association between preoperative risk factors and incident postoperative delirium in multivariate models. Electronic searches were conducted in PubMed, Embase, PsycINFO, CINAHL, Cochrane Library, Proquest Dissertations and Theses, and WorldCatDissertations. Hand searches were conducted in selected journals and their supplements.Search yielded 6380 titles and abstracts from electronic databases and 72 titles from hand searches, and 10 studies met inclusion criteria. The following risk factors were significant in bivariate models: cognitive impairment, age, gender, institutionalization, functional impairment, body mass index (BMI), albumin, comorbidities, American Society of Anesthesiologist classification, acute medical conditions, polypharmacy, and vision impairment. Among all of these risk factors, cognitive impairment most consistently remained statistically significant after adjusting for other risk factors in multivariate models, followed by BMI/albumin and multiple comorbidities.In our systematic review, cognitive impairment was one of the strongest preoperative risk factors for postoperative delirium after hip fracture surgery. Preoperative cognitive assessment may be one of the most useful methods of identifying those who are at high risk for postoperative delirium and prioritizing delivery of delirium prevention measures.


Hagedorn T.J.,Institute of Aging Research | Dufour A.B.,Institute of Aging Research | Dufour A.B.,Harvard University | Riskowski J.L.,Institute of Aging Research | And 6 more authors.
PLoS ONE | Year: 2013

Introduction:Foot disorders are common among older adults and may lead to outcomes such as falls and functional limitation. However, the associations of foot posture and foot function to specific foot disorders at the population level remain poorly understood. The purpose of this study was to assess the relation between specific foot disorders, foot posture, and foot function.Methods:Participants were from the population-based Framingham Foot Study. Quintiles of the modified arch index and center of pressure excursion index from plantar pressure scans were used to create foot posture and function subgroups. Adjusted odds ratios of having each specific disorder were calculated for foot posture and function subgroups relative to a referent 3 quintiles.Results:Pes planus foot posture was associated with increased odds of hammer toes and overlapping toes. Cavus foot posture was not associated with the foot disorders evaluated. Odds of having hallux valgus and overlapping toes were significantly increased in those with pronated foot function, while odds of hallux valgus and hallux rigidus were significantly decreased in those with supinated function.Conclusions:Foot posture and foot function were associated with the presence of specific foot disorders. © 2013 Hannan et al.


Oh E.S.,Johns Hopkins University | Sieber F.E.,Johns Hopkins University | Leoutsakos J.-M.,Johns Hopkins University | Inouye S.K.,Institute of Aging Research | And 2 more authors.
Journal of the American Geriatrics Society | Year: 2016

Objectives: To describe the differences observed in risk factors for delirium and outcomes between men and women undergoing hip fracture repair surgery. Design: Prospective cohort study. Setting: Academic medical center. Participants: Individuals with acute hip fracture admitted to an academic medical center (N = 431). Measurements: Information on preoperative demographic characteristics, medical history, laboratory results, and postoperative outcomes was obtained according to history and chart review. Delirium was assessed using the Confusion Assessment Method. Results: The overall incidence of postoperative delirium was 34%, with men more likely to experience postoperative delirium (44.8%) than women (30.2%) (P =.004). Male sex was associated with postoperative delirium in individuals with hip fracture, even after adjusting for other preoperative risk factors. Other significant preoperative risk factors included age, dementia, Parkinson's disease, and American Society of Anesthesiologists classification. Men were also more likely to experience other postoperative complications and have longer hospital length of stay. Conclusion: Men are at higher risk of postoperative delirium after hip fracture repair than women and have more postoperative surgical complications. Their higher risk of postoperative delirium may be due to their underlying preoperative disease severity. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society


PubMed | Institute of Aging Research
Type: Journal Article | Journal: PloS one | Year: 2013

Foot disorders are common among older adults and may lead to outcomes such as falls and functional limitation. However, the associations of foot posture and foot function to specific foot disorders at the population level remain poorly understood. The purpose of this study was to assess the relation between specific foot disorders, foot posture, and foot function.Participants were from the population-based Framingham Foot Study. Quintiles of the modified arch index and center of pressure excursion index from plantar pressure scans were used to create foot posture and function subgroups. Adjusted odds ratios of having each specific disorder were calculated for foot posture and function subgroups relative to a referent 3 quintiles.Pes planus foot posture was associated with increased odds of hammer toes and overlapping toes. Cavus foot posture was not associated with the foot disorders evaluated. Odds of having hallux valgus and overlapping toes were significantly increased in those with pronated foot function, while odds of hallux valgus and hallux rigidus were significantly decreased in those with supinated function.Foot posture and foot function were associated with the presence of specific foot disorders.


News Article | September 28, 2016
Site: www.chromatographytechniques.com

UCLA geneticist Steve Horvath led a team of 65 scientists in seven countries to record age-related changes to human DNA, calculate biological age and estimate a person's lifespan. A higher biological age—regardless of chronological age—consistently predicted an earlier death. The findings are published in today's edition of the journal Aging. "Our research reveals valuable clues into what causes human aging, marking a first step toward developing targeted methods to slow the process," said principal investigator Horvath, a professor of human genetics and biostatistics at UCLA's David Geffen School of Medicine and Fielding School of Public Health. Drawing on 13 sets of data, including the landmark Framingham Heart Study and Women's Health Initiative, a consortium of 25 institutions analyzed the DNA in blood samples collected from more than 13,000 people in the United States and Europe. Applying a variety of molecular methods, including an epigenetic clock developed by Horvath in 2013, the scientists measured the aging rates of each individual. The clock calculates the aging of blood and other tissues by tracking methylation, a natural process that chemically alters DNA over time. By comparing chronological age to the blood's biological age, the scientists used the clock to predict each person's life expectancy. "We were stunned to see that the epigenetic clock was able to predict the lifespans of Caucasians, Hispanics and African-Americans," said first author Brian Chen, a postdoctoral fellow at the National Institute on Aging. "This rang true even after adjusting for traditional risk factors like age, gender, smoking, body-mass index, disease history and blood cell counts." The group's findings, however, don't bode well for everyone. "We discovered that five percent of the population ages at a faster biological rate, resulting in a shorter life expectancy," Horvath said. "Accelerated aging increases these adults' risk of death by 50 percent at any age." For example, two 60-year-old men, Peter and Joe, both smoke to deal with high stress. Peter's epigenetic aging rate ranks in the top five percent, while Joe's aging rate is average. The likelihood of Peter dying within the next 10 years is 75 percent compared to 60 percent for Joe. The preliminary finding may explain why some individuals die young – even when they follow a nutritious diet, exercise regularly, drink in moderation and don't smoke. "While a healthful lifestyle may help extend life expectancy, our innate aging process prevents us from cheating death forever," Horvath emphasized. "Yet risk factors like smoking, diabetes and high blood pressure still predict mortality more strongly than one's epigenetic aging rate." Scientists have long searched to identify biomarkers for biological age, according to co-author Douglas Kiel, a professor at Harvard Medical School and a senior scientist for the Institute of Aging Research at Hebrew SeniorLife. "In geriatric medicine, we are always struck by the difference between our patients' chronological age and how old they appear physiologically," said Kiel. "This study validates the use of DNA methylation as a biomarker for biological age. And if we can prove that DNA methylation accelerates aging, we can devise strategies to slow the rate and maximize a person's years of good health." The precise role of epigenetic changes in aging and death, however, remains unknown, said co-author Themistocles Assimes, an assistant professor of cardiovascular medicine at Stanford University School of Medicine. "Do the epigenetic changes associated with chronological aging directly cause death in older people?" said Assimes. "Perhaps they merely enhance the development of certain diseases—or cripple one's ability to resist the progression of disease after it has taken root. Future research is needed to address these questions." Larger studies focused only on cases with well-documented causes of death will help scientists tease out the relationship between epigenetic age and specific diseases, he added. By 2017, according to the World Health Organization, the number of people worldwide over age 65 will outnumber those under age 5 for the first time in recorded history. By 2050, the proportion of the global population over 60 will double from 11 to 22 percent. Many countries will be ill-prepared to keep pace with the high costs associated with disease and disability as more people live longer, said Horvath. "We must find interventions that prolong healthy living by five to 20 years. We don't have time, however, to follow a person for decades to test whether a new drug works." said Horvath. "The epigenetic clock would allow scientists to quickly evaluate the effect of anti-aging therapies in only three years." The University of California has applied for a provisional patent on the epigenetic clock.

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