Over the past three decades, considerable effort has been dedicated to quantifying the pace of ag... more Over the past three decades, considerable effort has been dedicated to quantifying the pace of ageing yet identifying the most essential metrics of ageing remains challenging due to lack of comprehensive measurements and heterogeneity of the ageing processes. Most of the previously proposed metrics of ageing have been emerged from cross-sectional associations with chronological age and predictive accuracy of mortality, thus lacking a conceptual model of functional or phenotypic domains. Further, such models may be biased by selective attrition and are unable to address underlying biological constructs contributing to functional markers of age-related decline. Using longitudinal data from the Baltimore Longitudinal Study of Aging (BLSA), we propose a conceptual framework to identify metrics of ageing that may capture the hierarchical and temporal relationships between functional ageing, phenotypic ageing and biological ageing based on four hypothesized domains: body composition, energy regulation, homeostatic mechanisms and neurodegeneration/neuroplasticity. We explored the longitudinal trajectories of key variables within these phenotypes using linear mixedeffects models and more than 10 years of data. Understanding the longitudinal trajectories across these domains in the BLSA provides a reference for researchers, informs future refinement of the phenotypic ageing framework and establishes a solid foundation for future models of biological ageing.
Telomeres provide a key mechanism for protecting the integrity of chromosomes and their attritio... more Telomeres provide a key mechanism for protecting the integrity of chromosomes and their attrition after cell division and during aging are evident in lymphocytes. However, the significance of telomere shortening in age-associated decline of immune function is unknown. We selected 22 HLA-A2(+) healthy older adults who have relatively short or long telomere lengths to compare their antibody response against the influenza vaccine, and their CD8(+) T cell response against an influenza antigen. B cells from individuals with a robust antibody response to the influenza vaccine had significantly longer telomeres than those with a poor antibody response. Monocyte-derived antigen-presenting cells of both short and long telomere groups induced similar expansions of influenza M1-specific CD8(+) T cells. Vaccination did not increase M1-specific CD8(+) T cells in blood, however, M1-specific CD8(+) T cells from the long telomere group exhibited significantly better expansion in vitro compared t...
Journal of the American Dietetic Association, 2004
LEARNING OUTCOME: Participants will compare data on the hydrophilic antioxidant content of fresh ... more LEARNING OUTCOME: Participants will compare data on the hydrophilic antioxidant content of fresh tomatoes and processed tomato products, which will provide better information for dietary decisions. TEXT: Dietary antioxidants are a mechanism for disease prevention. Although many foods have been assayed to determine their antioxidant content, few studies have investigated differences in antioxidant content by comparing processed with fresh varieties. Fruits and vegetables may exhibit variations in antioxidant concentrations, even among cultivars of a given species. Antioxidant content of foods may be affected by food processing procedures. Therefore, the purpose of this study was to determine if there are differences in the hydrophilic antioxidant content of various fresh and processed tomato products. Antioxidants were measured using a hydrophilic antioxidant assay based on enzymatically generated ABTS (2,2Ј-azino-bis-(3-ethylbenzthiazonline-6-sulfonic acid)) radicals and their decoloration in the presence of antioxidants. Extracts were prepared from fresh, frozen and thawed, microwave heated, and whole canned tomatoes. Liquid drained from thawed tomatoes and from canned tomatoes was also analyzed for antioxidant content. Finally, tomato paste was extracted and analyzed for antioxidant content. Tomato paste contained the greatest concentration of antioxidants, with over three times the concentration of fresh tomatoes. Statistically significant differences in antioxidant concentrations were observed among tomato cultivars. Freezing and thawing had little effect on antioxidant concentration, however, both the liquid from thawed frozen tomatoes and the liquid in canned tomatoes had substantial antioxidant content. These results should be useful to dietitians who recommend various preparation and processing methods of specific foods to their clients. Knowledge of the antioxidant content is important in helping clients make the best food intake decisions to improve their health and prevent diseases.
Journal of the American Dietetic Association, 2007
Learning Outcome: Describe benefits of telephone follow-up for weight stabilization and symptom m... more Learning Outcome: Describe benefits of telephone follow-up for weight stabilization and symptom management of patients receiving outpatient intravenous chemotherapy. Text: Due to varying treatment schedules, cancer patients receiving outpatient chemotherapy are difficult to follow in a timely manner. The purpose of the study was to improve consistency of follow-up by the registered dietitian (RD) by implementing telephone "visits" with patients undergoing intravenous chemotherapy. At baseline, 37% of intravenous chemotherapy patients were followed by the RD. After implementation, patients not seen in clinic within 20 days were telephoned by the RD at home for reassessment. Sixty-six patients (31 male, 35 female, median age 63 ϩ 12 years) were monitored approximately 11 weeks (range 2-29) for weight status, resolution of nausea and vomiting, and timeliness of follow-up. Of the 66 subjects, 54 reported at least one of three symptoms -nausea and vomiting, decreased appetite, or weight loss. After follow-up by the RD, 67% reported resolution of nausea and vomiting, 70% reported improvements in appetite; and 71% reported weight stabilization. Comparisons (t-test) of percent usual body weight initially and percent usual body weight at the end of medical nutrition therapy (MNT) telephone visits were not statistically significant (pϭ0.782). Using Pearson's Product Moment Correlation, a weak negative relationship (rϭ Ϫ0.237) was found between number of weeks receiving MNT telephone visits and percent usual body weight at completion of MNT. Implementation of telephone visit interventions improved timely follow-up by 51% (88% of patients seen or visited on time). Results demonstrate that implementation of a telephone follow-up program can improve continuity of patient care and monitoring of intravenous chemotherapy patients.
•We examined the changes on body composition in 128 participants (BMI 2240) for 24 weeks. •DASH-S... more •We examined the changes on body composition in 128 participants (BMI 2240) for 24 weeks. •DASH-Style diet and exercise (DS; n=70) •Exercise only (EO, n=58) •Both groups received an exercise prescription recommending a minimum of: •moderate physical activity •15 minutes per session, progressing to 45 minutes •3 days per week progressing to 4 days per week by week 12. •They were provided support via once weekly meetings with an exercise physiologist for 12 weeks and biweekly thereafter. •The DS group also followed a standardized dietary approach consisting of: •a reduced calorie eating pattern •Incorporation of one commercially prepared healthy frozen meal and one other selected grocery item each day •dietary counseling from a dietician once weekly for 12 weeks and biweekly thereafter. Results
Previous in-vivo magnetic resonance imaging (MRI)-based studies of age-related differences in the... more Previous in-vivo magnetic resonance imaging (MRI)-based studies of age-related differences in the human brainstem have focused on volumetric morphometry. These investigations have provided pivotal insights into regional brainstem atrophy but have not addressed microstructural age-differences. However, growing evidence indicates the sensitivity of quantitative MRI to microstructural tissue changes in the brain. These studies have largely focused on the cerebrum, with very few MR investigations addressing age-dependent differences in the brainstem, in spite of its central role in the regulation of vital functions. Several studies indicate early brainstem alterations in a myriad of neurodegenerative diseases and dementias. The paucity of MR-focused investigations is likely due in part to the challenges imposed by the small structural scale of the brainstem itself as well as of substructures within, requiring accurate high-spatial resolution imaging studies. In this work, we applied our recently developed approach to high-resolution myelin water fraction (MWF) mapping, a proxy for myelin content, to investigate myelin differences with normal aging within the brainstem. In this cross-sectional investigation, we studied a large cohort (n = 125) of cognitively unimpaired participants spanning a wide age range (21-94 years) and found a decrease in myelination with age in most brainstem regions studied, while various regions exhibited a quadratic association between myelin and age. We believe that this study is the first investigation of MWF differences with normative aging in the adult brainstem. Further, our results provide reference MWF values.
Alzheimer's & dementia : the journal of the Alzheimer's Association, Jan 19, 2018
We investigated brain demyelination in aging, mild cognitive impairment (MCI), and dementia using... more We investigated brain demyelination in aging, mild cognitive impairment (MCI), and dementia using a direct magnetic resonance imaging marker of myelin. Brains of young and old controls, and old subjects with MCI, Alzheimer's disease, or vascular dementia were scanned using our recently developed myelin water fraction (MWF) mapping technique, which provides greatly improved accuracy over previous comparable methods. Maps of MWF, a direct and specific myelin measure, and relaxation times and magnetization transfer ratio, indirect and nonspecific measures, were constructed. MCI subjects showed decreased MWF compared with old controls. Demyelination was greater in Alzheimer's disease or vascular dementia. As expected, decreased MWF was accompanied by decreased magnetization transfer ratio and increased relaxation times. The young subjects showed greater myelin content than the old subjects. We believe this to be the first demonstration of myelin loss in MCI, Alzheimer's dise...
Mitochondrial function in human skeletal muscle declines with age. Most evidence for this decline... more Mitochondrial function in human skeletal muscle declines with age. Most evidence for this decline comes from studies that assessed mitochondrial function indirectly, and the impact of such deterioration with respect to physical function has not been clearly delineated. We hypothesized that mitochondrial respiration in permeabilized human muscle fibers declines with age and correlates with phosphocreatine postexercise recovery rate (kPCr), muscle performance, and aerobic fitness. Mitochondrial respiration was assessed by high-resolution respirometry in saponin-permeabilized fibers from vastus lateralis muscle biopsies of 38 participants from the Baltimore Longitudinal Study of Aging (BLSA; 21 men, age 24-91 years) who also had available measures of peak oxygen consumption (VO2max ) from treadmill tests, gait speed in different tasks, 31 P magnetic resonance spectroscopy, isokinetic knee extension, and grip strength. Results indicated a significant reduction in mitochondrial respirati...
ABSTRACT Coronary heart disease remains the leading killer of men and women in the United States.... more ABSTRACT Coronary heart disease remains the leading killer of men and women in the United States. Coronary heart disease also represents one of the quintessential lifestyle-related diseases. Many of the major risk factors for coronary heart disease, including elevated cholesterol, high blood pressure, cigarette smoking, an inactive lifestyle, and obesity, have very significant lifestyle-related components. In part I of this review, the authors discussed the rationale for using lifestyle medicine strategies as part of a comprehensive approach to preventing, reducing the risk, or treating coronary heart disease. In part II, the authors focus on practical strategies for incorporating lifestyle medicine techniques into clinical practice. The overall framework is based on the American College of Cardiology's Bethesda Conference, which places risk factors into 4 categories depending on the likelihood that modifying a particular risk factor will result in lowering the risk of coronary heart disease. The authors have similarly grouped lifestyle medicine strategies to explore how these interventions can be employed in each of the classes of interventions defined by the American College of Cardiology. Although the authors recognize that individual clinicians have time constraints which affect utilization of lifestyle medicine strategies, the best outcomes can be achieved by combining these interventions with more traditional modalities for reducing the risk, preventing, or treating coronary heart disease.
Cardiovascular diseases remain extremely common and the United States and are the single most com... more Cardiovascular diseases remain extremely common and the United States and are the single most common cause for death in both men and women. Many risk factors including cigarette smoking, elevated cholesterol, high blood pressure, obesity and in inactive lifestyle carry a significant lifestyle component. This fact is recognized in the National Guidelines for the Treatment of many risk factors for cardiovascular disease. Moreover, lifestyle intervention, in combination with proper medical and/or surgical therapy can play a significant role in the management of existing cardiovascular disease. In this review, we provide background and rationale for interventions to reduce the risk of coronary heart disease with a particular emphasis on intervening to improve lifestyle related issues. To achieve the best outcomes clinicians must be skilled not only in pharmacologic and surgical therapies but also in counseling patients on various lifestyle interventions to lower the risk of cardiovascular disease.
Over the past three decades, considerable effort has been dedicated to quantifying the pace of ag... more Over the past three decades, considerable effort has been dedicated to quantifying the pace of ageing yet identifying the most essential metrics of ageing remains challenging due to lack of comprehensive measurements and heterogeneity of the ageing processes. Most of the previously proposed metrics of ageing have been emerged from cross-sectional associations with chronological age and predictive accuracy of mortality, thus lacking a conceptual model of functional or phenotypic domains. Further, such models may be biased by selective attrition and are unable to address underlying biological constructs contributing to functional markers of age-related decline. Using longitudinal data from the Baltimore Longitudinal Study of Aging (BLSA), we propose a conceptual framework to identify metrics of ageing that may capture the hierarchical and temporal relationships between functional ageing, phenotypic ageing and biological ageing based on four hypothesized domains: body composition, energy regulation, homeostatic mechanisms and neurodegeneration/neuroplasticity. We explored the longitudinal trajectories of key variables within these phenotypes using linear mixedeffects models and more than 10 years of data. Understanding the longitudinal trajectories across these domains in the BLSA provides a reference for researchers, informs future refinement of the phenotypic ageing framework and establishes a solid foundation for future models of biological ageing.
Telomeres provide a key mechanism for protecting the integrity of chromosomes and their attritio... more Telomeres provide a key mechanism for protecting the integrity of chromosomes and their attrition after cell division and during aging are evident in lymphocytes. However, the significance of telomere shortening in age-associated decline of immune function is unknown. We selected 22 HLA-A2(+) healthy older adults who have relatively short or long telomere lengths to compare their antibody response against the influenza vaccine, and their CD8(+) T cell response against an influenza antigen. B cells from individuals with a robust antibody response to the influenza vaccine had significantly longer telomeres than those with a poor antibody response. Monocyte-derived antigen-presenting cells of both short and long telomere groups induced similar expansions of influenza M1-specific CD8(+) T cells. Vaccination did not increase M1-specific CD8(+) T cells in blood, however, M1-specific CD8(+) T cells from the long telomere group exhibited significantly better expansion in vitro compared t...
Journal of the American Dietetic Association, 2004
LEARNING OUTCOME: Participants will compare data on the hydrophilic antioxidant content of fresh ... more LEARNING OUTCOME: Participants will compare data on the hydrophilic antioxidant content of fresh tomatoes and processed tomato products, which will provide better information for dietary decisions. TEXT: Dietary antioxidants are a mechanism for disease prevention. Although many foods have been assayed to determine their antioxidant content, few studies have investigated differences in antioxidant content by comparing processed with fresh varieties. Fruits and vegetables may exhibit variations in antioxidant concentrations, even among cultivars of a given species. Antioxidant content of foods may be affected by food processing procedures. Therefore, the purpose of this study was to determine if there are differences in the hydrophilic antioxidant content of various fresh and processed tomato products. Antioxidants were measured using a hydrophilic antioxidant assay based on enzymatically generated ABTS (2,2Ј-azino-bis-(3-ethylbenzthiazonline-6-sulfonic acid)) radicals and their decoloration in the presence of antioxidants. Extracts were prepared from fresh, frozen and thawed, microwave heated, and whole canned tomatoes. Liquid drained from thawed tomatoes and from canned tomatoes was also analyzed for antioxidant content. Finally, tomato paste was extracted and analyzed for antioxidant content. Tomato paste contained the greatest concentration of antioxidants, with over three times the concentration of fresh tomatoes. Statistically significant differences in antioxidant concentrations were observed among tomato cultivars. Freezing and thawing had little effect on antioxidant concentration, however, both the liquid from thawed frozen tomatoes and the liquid in canned tomatoes had substantial antioxidant content. These results should be useful to dietitians who recommend various preparation and processing methods of specific foods to their clients. Knowledge of the antioxidant content is important in helping clients make the best food intake decisions to improve their health and prevent diseases.
Journal of the American Dietetic Association, 2007
Learning Outcome: Describe benefits of telephone follow-up for weight stabilization and symptom m... more Learning Outcome: Describe benefits of telephone follow-up for weight stabilization and symptom management of patients receiving outpatient intravenous chemotherapy. Text: Due to varying treatment schedules, cancer patients receiving outpatient chemotherapy are difficult to follow in a timely manner. The purpose of the study was to improve consistency of follow-up by the registered dietitian (RD) by implementing telephone "visits" with patients undergoing intravenous chemotherapy. At baseline, 37% of intravenous chemotherapy patients were followed by the RD. After implementation, patients not seen in clinic within 20 days were telephoned by the RD at home for reassessment. Sixty-six patients (31 male, 35 female, median age 63 ϩ 12 years) were monitored approximately 11 weeks (range 2-29) for weight status, resolution of nausea and vomiting, and timeliness of follow-up. Of the 66 subjects, 54 reported at least one of three symptoms -nausea and vomiting, decreased appetite, or weight loss. After follow-up by the RD, 67% reported resolution of nausea and vomiting, 70% reported improvements in appetite; and 71% reported weight stabilization. Comparisons (t-test) of percent usual body weight initially and percent usual body weight at the end of medical nutrition therapy (MNT) telephone visits were not statistically significant (pϭ0.782). Using Pearson's Product Moment Correlation, a weak negative relationship (rϭ Ϫ0.237) was found between number of weeks receiving MNT telephone visits and percent usual body weight at completion of MNT. Implementation of telephone visit interventions improved timely follow-up by 51% (88% of patients seen or visited on time). Results demonstrate that implementation of a telephone follow-up program can improve continuity of patient care and monitoring of intravenous chemotherapy patients.
•We examined the changes on body composition in 128 participants (BMI 2240) for 24 weeks. •DASH-S... more •We examined the changes on body composition in 128 participants (BMI 2240) for 24 weeks. •DASH-Style diet and exercise (DS; n=70) •Exercise only (EO, n=58) •Both groups received an exercise prescription recommending a minimum of: •moderate physical activity •15 minutes per session, progressing to 45 minutes •3 days per week progressing to 4 days per week by week 12. •They were provided support via once weekly meetings with an exercise physiologist for 12 weeks and biweekly thereafter. •The DS group also followed a standardized dietary approach consisting of: •a reduced calorie eating pattern •Incorporation of one commercially prepared healthy frozen meal and one other selected grocery item each day •dietary counseling from a dietician once weekly for 12 weeks and biweekly thereafter. Results
Previous in-vivo magnetic resonance imaging (MRI)-based studies of age-related differences in the... more Previous in-vivo magnetic resonance imaging (MRI)-based studies of age-related differences in the human brainstem have focused on volumetric morphometry. These investigations have provided pivotal insights into regional brainstem atrophy but have not addressed microstructural age-differences. However, growing evidence indicates the sensitivity of quantitative MRI to microstructural tissue changes in the brain. These studies have largely focused on the cerebrum, with very few MR investigations addressing age-dependent differences in the brainstem, in spite of its central role in the regulation of vital functions. Several studies indicate early brainstem alterations in a myriad of neurodegenerative diseases and dementias. The paucity of MR-focused investigations is likely due in part to the challenges imposed by the small structural scale of the brainstem itself as well as of substructures within, requiring accurate high-spatial resolution imaging studies. In this work, we applied our recently developed approach to high-resolution myelin water fraction (MWF) mapping, a proxy for myelin content, to investigate myelin differences with normal aging within the brainstem. In this cross-sectional investigation, we studied a large cohort (n = 125) of cognitively unimpaired participants spanning a wide age range (21-94 years) and found a decrease in myelination with age in most brainstem regions studied, while various regions exhibited a quadratic association between myelin and age. We believe that this study is the first investigation of MWF differences with normative aging in the adult brainstem. Further, our results provide reference MWF values.
Alzheimer's & dementia : the journal of the Alzheimer's Association, Jan 19, 2018
We investigated brain demyelination in aging, mild cognitive impairment (MCI), and dementia using... more We investigated brain demyelination in aging, mild cognitive impairment (MCI), and dementia using a direct magnetic resonance imaging marker of myelin. Brains of young and old controls, and old subjects with MCI, Alzheimer's disease, or vascular dementia were scanned using our recently developed myelin water fraction (MWF) mapping technique, which provides greatly improved accuracy over previous comparable methods. Maps of MWF, a direct and specific myelin measure, and relaxation times and magnetization transfer ratio, indirect and nonspecific measures, were constructed. MCI subjects showed decreased MWF compared with old controls. Demyelination was greater in Alzheimer's disease or vascular dementia. As expected, decreased MWF was accompanied by decreased magnetization transfer ratio and increased relaxation times. The young subjects showed greater myelin content than the old subjects. We believe this to be the first demonstration of myelin loss in MCI, Alzheimer's dise...
Mitochondrial function in human skeletal muscle declines with age. Most evidence for this decline... more Mitochondrial function in human skeletal muscle declines with age. Most evidence for this decline comes from studies that assessed mitochondrial function indirectly, and the impact of such deterioration with respect to physical function has not been clearly delineated. We hypothesized that mitochondrial respiration in permeabilized human muscle fibers declines with age and correlates with phosphocreatine postexercise recovery rate (kPCr), muscle performance, and aerobic fitness. Mitochondrial respiration was assessed by high-resolution respirometry in saponin-permeabilized fibers from vastus lateralis muscle biopsies of 38 participants from the Baltimore Longitudinal Study of Aging (BLSA; 21 men, age 24-91 years) who also had available measures of peak oxygen consumption (VO2max ) from treadmill tests, gait speed in different tasks, 31 P magnetic resonance spectroscopy, isokinetic knee extension, and grip strength. Results indicated a significant reduction in mitochondrial respirati...
ABSTRACT Coronary heart disease remains the leading killer of men and women in the United States.... more ABSTRACT Coronary heart disease remains the leading killer of men and women in the United States. Coronary heart disease also represents one of the quintessential lifestyle-related diseases. Many of the major risk factors for coronary heart disease, including elevated cholesterol, high blood pressure, cigarette smoking, an inactive lifestyle, and obesity, have very significant lifestyle-related components. In part I of this review, the authors discussed the rationale for using lifestyle medicine strategies as part of a comprehensive approach to preventing, reducing the risk, or treating coronary heart disease. In part II, the authors focus on practical strategies for incorporating lifestyle medicine techniques into clinical practice. The overall framework is based on the American College of Cardiology's Bethesda Conference, which places risk factors into 4 categories depending on the likelihood that modifying a particular risk factor will result in lowering the risk of coronary heart disease. The authors have similarly grouped lifestyle medicine strategies to explore how these interventions can be employed in each of the classes of interventions defined by the American College of Cardiology. Although the authors recognize that individual clinicians have time constraints which affect utilization of lifestyle medicine strategies, the best outcomes can be achieved by combining these interventions with more traditional modalities for reducing the risk, preventing, or treating coronary heart disease.
Cardiovascular diseases remain extremely common and the United States and are the single most com... more Cardiovascular diseases remain extremely common and the United States and are the single most common cause for death in both men and women. Many risk factors including cigarette smoking, elevated cholesterol, high blood pressure, obesity and in inactive lifestyle carry a significant lifestyle component. This fact is recognized in the National Guidelines for the Treatment of many risk factors for cardiovascular disease. Moreover, lifestyle intervention, in combination with proper medical and/or surgical therapy can play a significant role in the management of existing cardiovascular disease. In this review, we provide background and rationale for interventions to reduce the risk of coronary heart disease with a particular emphasis on intervening to improve lifestyle related issues. To achieve the best outcomes clinicians must be skilled not only in pharmacologic and surgical therapies but also in counseling patients on various lifestyle interventions to lower the risk of cardiovascular disease.
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Papers by Linda Zukley