Bio

Bio


Dr. Liu and her research program are dedicated to improving the lives of older adults with kidney disease. Currently her research focuses on mobility, which is the ability to move safely and reliably from one place to another. In older adults, poor mobility strongly predicts future disability and death. Retaining mobility has been cited by older adults as fundamental to quality to life; yet many older persons with kidney disease, especially those with late stage chronic kidney disease or outright kidney failure, have trouble just walking across the room or transferring to a chair. Dually trained in geriatric medicine and epidemiology, Dr. Liu also has significant expertise in older adult clinical trials, including safety trials of novel agents as well as intervention studies to reduce infections in older populations.

Academic Appointments


Boards, Advisory Committees, Professional Organizations


  • Associate Editor, BMC Nephrology (2019 - Present)
  • Long-Term Care Reopening Workgroup, Executive Office of Health and Human Services, Commonwealth of Massachusetts (2020 - Present)

Professional Education


  • Fellow, Boston University School of Medicine, Geriatric Medicine (2011)
  • MS, Boston University School of Public Health, Epidemiology (2011)
  • Resident, Boston University School of Medicine, Internal Medicine/Primary Care (2008)
  • MD, Temple University School of Medicine, Medicine (2005)
  • BA, Brown University, Biology (1996)

Publications

All Publications


  • Translating the Lifestyle Interventions and Independence for Elders Clinical Trial to Older Adults in a Real-World Community-Based Setting. The journals of gerontology. Series A, Biological sciences and medical sciences Reid, K. F., Laussen, J., Bhatia, K., Englund, D. A., Kirn, D. R., Price, L. L., Manini, T. M., Liu, C. K., Kowaleski, C., Fielding, R. A. 2019; 74 (6): 924?28

    Abstract

    The Lifestyle Interventions and Independence for Elders (LIFE) clinical trial demonstrated that a structured program of physical activity (PA) reduced mobility-disability in older adults by up to 28%. It remains unknown whether the benefits of LIFE PA can be translated to older adults at risk for mobility-disability in real-world community-based settings. To address this knowledge gap, we conducted the ENhancing independence using Group-based community interventions for healthy AGing in Elders (ENGAGE) pilot study and examined the safety, feasibility, and preliminary effectiveness of translating LIFE PA to a community-based senior center.Forty older adults with severe lower extremity functional limitations (age: 76.9 ± 7.3 years; body mass index: 32.7 ± 8 kg/m2; 85% female; short physical performance battery score: 6.3 ± 2.2) were randomized to 24 weeks of PA or a health education control intervention.Community-based PA was safe (serious adverse events: PA vs health education, 0:2; nonserious adverse events: PA vs health education, 3:1) and participants successfully adhered to the PA intervention (65.2%). Compared to health education, PA participants who attended ?25% of scheduled visits had meaningful and sustained short physical performance battery improvements at follow-up (between group short physical performance battery score differences: ~0.7 units).ENGAGE has demonstrated the preliminary safety, feasibility, and effectiveness of LIFE PA in a real-world community-based setting. Larger-scale translational studies are needed to further disseminate the benefits of LIFE PA to vulnerable older adults in a variety of community-based settings.

    View details for DOI 10.1093/gerona/gly152

    View details for PubMedID 30010808

    View details for PubMedCentralID PMC6521918

  • Muscle strength is increased in mice that are colonized with microbiota from high-functioning older adults. Experimental gerontology Fielding, R. A., Reeves, A. R., Jasuja, R., Liu, C., Barrett, B. B., Lustgarten, M. S. 2019; 127: 110722

    Abstract

    Evidence in support of a gut-muscle axis has been reported in rodents, but studies in older adult humans are limited. Accordingly, the primary goals of the present study were to compare gut microbiome composition in older adults that differed in terms of the percentage of whole body lean mass and physical functioning (high-functioning, HF, n?=?18; low-functioning, LF, n?=?11), and to evaluate the causative role of the gut microbiome on these variables by transferring fecal samples from older adults into germ-free mice. Family-level Prevotellaceae, genus-level Prevotella and Barnesiella, and the bacterial species Barnesiella intestinihominis were higher in HF older adults at the initial study visit, at a 1-month follow-up visit, in HF human fecal donors, and in HF-colonized mice, when compared with their LF counterparts. Grip strength was significantly increased by 6.4% in HF-, when compared with LF-colonized mice. In contrast, despite significant differences for the percentage of whole body lean mass and physical functioning when comparing the human fecal donors, the percentage of whole body lean mass and treadmill endurance capacity were not different when comparing human microbiome-containing mice. In sum, these data suggest a role for gut bacteria on the maintenance of muscle strength, but argue against a role for gut bacteria on the maintenance of the percentage of whole body lean mass or endurance capacity, findings that collectively add to elucidation of the gut-muscle axis in older adults.

    View details for DOI 10.1016/j.exger.2019.110722

    View details for PubMedID 31493521

    View details for PubMedCentralID PMC6823114

  • Effect of Losartan and Fish Oil on Plasma IL-6 and Mobility in Older Persons. The ENRGISE Pilot Randomized Clinical Trial. The journals of gerontology. Series A, Biological sciences and medical sciences Pahor, M., Anton, S. D., Beavers, D. P., Cauley, J. A., Fielding, R. A., Kritchevsky, S. B., Leeuwenburgh, C., Lewis, K. H., Liu, C. K., Lovato, L. C., Lu, J., Manini, T. M., McDermott, M. M., Miller, M. E., Newman, A. B., Radziszewska, B., Stowe, C. L., Tracy, R. P., Walkup, M. P., Wu, S. S., Ambrosius, W. T. 2019; 74 (10): 1612?19

    Abstract

    Low-grade chronic inflammation, characterized by elevations in plasma Interleukin-6 (IL-6), is an independent risk factor of impaired mobility in older persons. Angiotensin receptor blockers and omega-3 polyunsaturated fatty acids (?-3) may reduce IL-6 and may potentially improve physical function. To assess the main effects of the angiotensin receptor blocker losartan and ?-3 as fish oil on IL-6 and 400 m walking speed, we conducted the ENRGISE Pilot multicenter randomized clinical trial.The ENRGISE Pilot enrolled participants between April 2016 and June 2017, who participated for 12 months. Participants were aged ?70 years with mobility impairment, had IL-6 between 2.5 and 30 pg/mL, and were able to walk 400 m at baseline. Participants were randomized in three strata 2 × 2 factorial to: (i) losartan 50-100 mg/d or placebo (n = 43), (ii) fish oil 1,400-2,800 mg/d or placebo (n = 180), and (iii) with both (n = 66).Two hundred eighty-nine participants were randomized (mean age 78.3 years, 47.4% women, 17.0% black). There was no effect of losartan (difference of means = -0.065 ± 0.116 [SE], 95% confidence interval [CI]: -0.293-0.163, p = .58) or fish oil (-0.020 ± 0.077, 95% CI: -0.171-0.132, p = .80) on the log of IL-6. Similarly, there was no effect of losartan (-0.025 ± 0.026, 95% CI: -0.076-0.026, p = .34) or fish oil (0.010 ± 0.017, 95% CI: -0.025-0.044, p = .58) on walking speed (m/s).These results do not support the use of these interventions to prevent mobility loss in older adults at risk of disability with low-grade chronic inflammation.Clinicaltrials.gov NCT02676466.

    View details for DOI 10.1093/gerona/gly277

    View details for PubMedID 30541065

    View details for PubMedCentralID PMC6748815

  • Progressive Resistance Training Improves Torque Capacity and Strength in Mobility-Limited Older Adults. The journals of gerontology. Series A, Biological sciences and medical sciences Englund, D. A., Price, L. L., Grosicki, G. J., Iwai, M., Kashiwa, M., Liu, C., Reid, K. F., Fielding, R. A. 2019; 74 (8): 1316?21

    Abstract

    Progressive resistance training (PRT) is consistently shown to improve muscle strength in older adults. The efficacy of PRT to improve muscle fatigue in older adults with demonstrated mobility limitations remains unclear.Mobility-limited (Short Physical Performance Battery [SPPB] ? 9) older adults (age 70-92 years) were recruited for this study and randomized to either PRT or home-based flexibility (FLEX) 3 d/wk for 12 weeks. Muscle fatigue and strength outcomes were assessed at baseline and 12 weeks. The primary outcome was torque capacity, a composite measure of strength and fatigue, defined as the sum of peak torques from an isokinetic fatigue test.Seventy participants were randomized (mean [SD] age 78.9 [5.4] years; 60% female; mean [SD] SPPB 7.5 [1.6]). At follow-up, the PRT group improved significantly in torque capacity, mean between-group difference (95% confidence interval) 466.19 (138.4, 793.97) Nm (p = .006), and maximal strength 127.3 (60.96, 193.61) Nm (p = .0003), when compared with FLEX group. Neither group demonstrated significant changes in muscle fatigue or torque variability.Twelve weeks of PRT improved torque capacity, as well as strength in mobility-limited older adults. These results demonstrate PRT improves multiple age-related muscular impairments.

    View details for DOI 10.1093/gerona/gly199

    View details for PubMedID 30165595

    View details for PubMedCentralID PMC6625591

  • Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trial BMC MEDICINE Liu, Z., Hsu, F., Trombetti, A., King, A. C., Liu, C. K., Manini, T. M., Fielding, R. A., Pahor, M., Newman, A. B., Kritchevsky, S., Gill, T. M., LIFE Study Investigators 2018; 16
  • A Comparison of Self-report Indices of Major Mobility Disability to Failure on the 400-m Walk Test: The LIFE Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Chen, H., Rejeski, W., Gill, T. M., Guralnik, J., King, A. C., Newman, A., Blair, S. N., Conroy, D., Liu, C., Manini, T. M., Pahor, M., Ambrosius, W. T., Miller, M. E., LIFE Study 2018; 73 (4): 513?18

    Abstract

    The objective assessment of major mobility disability (objective MMD) by a 400-m walk test (400 MWT) is important but not always practical. Previous research on the relationship between self-reported MMD (SR MMD) and objective MMD is sparse and limited to cross-sectional data.We evaluated agreement between SR MMD and objective MMD using longitudinal data from the Lifestyle Interventions for Elders (LIFE) study. The SR MMD indices were defined based on having a lot of difficulty or inability to walk a quarter of a mile (SR-1/4MILE), walk several blocks (SR-BLOCKS), and climb one flight of stairs (SR-STAIRS).Using objective MMD as the gold standard, SR-1/4MILE and SR-BLOCKS had relatively low sensitivity (around 0.4) and high specificity (around 0.9) for prevalence. Their overall sensitivity and specificity for cumulative incident objective MMD were approximately 0.6 and 0.8, respectively. While the annual probability of staying MMD free was similar for objective MMD, SR-1/4MILE, and SR-BLOCKS (90% for all), the probability of recovering from SR MMD was higher (50%) than that of objective MMD (22%). The development of objective MMD (439 events), SR-1/4MILE (356 events), and SR-BLOCKS (379 events) had a similar trajectory over time with substantially overlapping survival curves. SR-STAIRS generally did not agree well with objective MMD. Incorporating SR-STAIRS with either SR-1/4MILE or SR-BLOCKS did not significantly improve the agreement between SR MMD and objective MMD.Simple SR-1/4MILE and SR-BLOCKS are reasonable candidates to define MMD if the primary outcome of interest is incident MMD.

    View details for PubMedID 28958023

    View details for PubMedCentralID PMC5861858

  • Effect of Physical Activity on Frailty Secondary Analysis of a Randomized Controlled Trial ANNALS OF INTERNAL MEDICINE Trombetti, A., Hars, M., Hsu, F., Reid, K. F., Church, T. S., Gill, T. M., King, A. C., Liu, C. K., Manini, T. M., McDermott, M. M., Newman, A. B., Rejeski, W., Guralnik, J. M., Pahor, M., Fielding, R. A., LIFE Study Investigators 2018; 168 (5): 309-+

    Abstract

    Limited evidence suggests that physical activity may prevent frailty and associated negative outcomes in older adults. Definitive data from large long-term randomized trials are lacking.To determine whether a long-term, structured, moderate-intensity physical activity program is associated with a lower risk for frailty and whether frailty status alters the effect of physical activity on the reduction in major mobility disability (MMD) risk.Multicenter, single-blind, randomized trial.8 centers in the United States.1635 community-dwelling adults, aged 70 to 89 years, with functional limitations.A structured, moderate-intensity physical activity program incorporating aerobic, resistance, and flexibility activities or a health education program consisting of workshops and stretching exercises.Frailty, as defined by the SOF (Study of Osteoporotic Fractures) index, at baseline and 6, 12, and 24 months, and MMD, defined as the inability to walk 400 m, for up to 3.5 years.Over 24 months of follow-up, the risk for frailty (n = 1623) was not statistically significantly different in the physical activity versus the health education group (adjusted prevalence difference, -0.021 [95% CI, -0.049 to 0.007]). Among the 3 criteria of the SOF index, the physical activity intervention was associated with improvement in the inability to rise from a chair (adjusted prevalence difference, -0.050 [CI, -0.081 to -0.020]). Baseline frailty status did not modify the effect of physical activity on reducing incident MMD (P for interaction = 0.91).Frailty status was neither an entry criterion nor a randomization stratum.A structured, moderate-intensity physical activity program was not associated with a reduced risk for frailty over 2 years among sedentary, community-dwelling older adults. The beneficial effect of physical activity on the incidence of MMD did not differ between frail and nonfrail participants.National Institute on Aging, National Institutes of Health.

    View details for PubMedID 29310138

  • Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis. Ageing research reviews Custodero, C., Mankowski, R. T., Lee, S. A., Chen, Z., Wu, S., Manini, T. M., Hincapie Echeverri, J., Sabbà, C., Beavers, D. P., Cauley, J. A., Espeland, M. A., Fielding, R. A., Kritchevsky, S. B., Liu, C. K., McDermott, M. M., Miller, M. E., Tracy, R. P., Newman, A. B., Ambrosius, W. T., Pahor, M., Anton, S. D. 2018; 46: 42?59

    Abstract

    Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and C-reactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials. Six compounds met all five inclusion criteria for our systematic review and meta-analysis: angiotensin II receptor blockers (ARBs), metformin, omega-3, probiotics, resveratrol and vitamin D. We searched in MEDLINE, PubMed and EMBASE database until January 2017. A total of 49 articles fulfilled the selection criteria. Effect size of each study and pooled effect size for each compound were measured by the standardized mean difference. I2 was computed to measure heterogeneity of effects across studies. The following compounds showed a significant small to large effect in reducing IL-6 levels: probiotics (-0.68?pg/ml), ARBs (-0.37?pg/ml) and omega-3 (-0.19?pg/ml). For CRP, a significant small to medium effect was observed with probiotics (-0.43?mg/L), ARBs (-0.2?mg/L), omega-3 (-0.17?mg/L) and metformin (-0.16?mg/L). Resveratrol and vitamin D were not associated with any significant reductions in either biomarker. These results suggest that nutritional and pharmaceutical compounds can significantly reduce established biomarkers of systemic inflammation in middle-age and older adults. The findings should be interpreted with caution, however, due to the evidence of heterogeneity across the studies.

    View details for DOI 10.1016/j.arr.2018.05.004

    View details for PubMedID 29803716

    View details for PubMedCentralID PMC6235673

  • Exercise's effect on mobility disability in older adults with and without obesity: The LIFE study randomized clinical trial OBESITY Kritchevsky, S. B., Lovato, L., Handing, E. P., Blair, S., Botoseneanu, A., Guralnik, J. M., Liu, C., King, A., Marsh, A. P., Pahor, M., Rejeski, W., Spring, B., Manini, T. 2017; 25 (7): 1199?1205

    Abstract

    Some data suggest that obesity blunts the benefits of exercise on mobility in older adults. This study tested the homogeneity of the effect of a physical activity intervention on major mobility disability (MMD) across baseline obesity classifications in the Lifestyle Interventions and Independence for Elders (LIFE) Study. LIFE randomized 1,635 sedentary men and women aged 70 to 89 years to a moderate-intensity physical activity (PA) or health education program.MMD, defined as the inability to walk 400 m, was determined over an average follow-up of 2.6 years. Participants were divided into four subgroups: (1) nonobese (BMI??102 cm [men],?>?88?cm [women]; n?=?434); (3) class 1 obesity (30 kg/m2 ???BMI?

    View details for PubMedID 28653499

    View details for PubMedCentralID PMC5567861

  • The Effect of Chronic Kidney Disease on a Physical Activity Intervention: Impact on Physical Function, Adherence, and Safety. Journal of clinical nephrology and renal care Liu, C. K., Milton, J., Hsu, F. C., Beavers, K. M., Yank, V., Church, T., Shegog, J. D., Kashaf, S., Nayfield, S., Newman, A., Stafford, R. S., Nicklas, B., Weiner, D. E., Fielding, R. A. 2017; 3 (1)

    Abstract

    Because chronic kidney disease (CKD) is associated with muscle wasting, older adults with CKD are likely to have physical function deficits. Physical activity can improve these deficits, but whether CKD attenuates the benefits is unknown. Our objective was to determine if CKD modified the effect of a physical activity intervention in older adults.This is an exploratory analysis of the LIFE-P study, which compared a 12-month physical activity program (PA) to a successful aging education program (SA) in older adults. CKD was defined as a baseline eGFR < 60 mL/min/1.73 m2. We examined the Short Physical Performance Battery (SPPB) at baseline, 6 and 12 months. Secondary outcomes included serious adverse events (SAE) and adherence to intervention frequency. Linear mixed models were adjusted for age, sex, diabetes, hypertension, CKD, intervention, site, visit, baseline SPPB, and interactions of intervention and visit and of intervention, visit, and baseline CKD.The sample included 368 participants. CKD was present in 105 (28.5%) participants with a mean eGFR of 49.2 ± 8.1 mL/min/1.73 m2. Mean SPPB was 7.38 ± 1.41 in CKD participants; 7.59 ± 1.44 in those without CKD (p = 0.20). For CKD participants in PA, 12-month SPPBs increased to 8.90 (95% CI 8.32, 9.47), while PA participants without CKD increased to 8.40 (95% CI 8.01, 8.79, p = 0.43). For CKD participants in SA, 12-month SPPBs increased to 7.67 (95% CI 7.07, 8.27), while participants without CKD increased to 8.12 (95% CI 7.72, 8.52, p = 0.86). Interaction between CKD and intervention was non-significant (p = 0.88). Number and type of SAEs were not different between CKD and non-CKD participants (all p > 0.05). In PA, adherence for CKD participants was 65.5 ± 25.4%, while for those without CKD was 74.0 ± 22.2% (p = 0.12).Despite lower adherence, older adults with CKD likely derive clinically meaningful benefits from physical activity with no apparent impact on safety, compared to those without CKD.

    View details for PubMedID 29745380

  • ENabling Reduction of Low-grade Inflammation in SEniors Pilot Study: Concept, Rationale, and Design. Journal of the American Geriatrics Society Manini, T. M., Anton, S. D., Beavers, D. P., Cauley, J. A., Espeland, M. A., Fielding, R. A., Kritchevsky, S. B., Leeuwenburgh, C., Lewis, K. H., Liu, C., McDermott, M. M., Miller, M. E., Tracy, R. P., Walston, J. D., Radziszewska, B., Lu, J., Stowe, C., Wu, S., Newman, A. B., Ambrosius, W. T., Pahor, M. 2017; 65 (9): 1961?68

    Abstract

    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.The ENabling Reduction of low-Grade Inflammation in SEniors (ENRGISE) Pilot Study was a multicenter, double-blind, placebo-controlled randomized pilot trial of two interventions to reduce IL-6 levels.Five university-based research centers.Target enrollment was 300 men and women aged 70 and older with an average plasma IL-6 level between 2.5 and 30 pg/mL measured twice at least 1 week apart. Participants had low to moderate physical function, defined as self-reported difficulty walking one-quarter of a mile or climbing a flight of stairs and usual walk speed of less than 1 m/s on a 4-m usual-pace walk.Participants were randomized to losartan, omega-3 fish oil (?-3), combined losartan and ?-3, or placebo. Randomization was stratified depending on eligibility for each group. A titration schedule was implemented to reach a dose that was safe and effective for IL-6 reduction. Maximal doses were 100 mg/d for losartan and 2.8 g/d for ?-3.IL-6, walking speed over 400 m, physical function (Short Physical Performance Battery), other inflammatory markers, safety, tolerability, frailty domains, and maximal leg strength were measured.Results from the ENRGISE Pilot Study will provide recruitment yields, feasibility, medication tolerance and adherence, and preliminary data to help justify a sample size for a more definitive randomized trial.The ENRGISE Pilot Study will inform a larger subsequent trial that is expected to have important clinical and public health implications for the growing population of older adults with low-grade chronic inflammation and mobility limitations.

    View details for DOI 10.1111/jgs.14965

    View details for PubMedID 28734043

    View details for PubMedCentralID PMC5642998

  • Effect of Structured Physical Activity on Respiratory Outcomes in Sedentary Elderly Adults with Mobility Limitations. Journal of the American Geriatrics Society Vaz Fragoso, C. A., Beavers, D. P., Anton, S. D., Liu, C. K., McDermott, M. M., Newman, A. B., Pahor, M., Stafford, R. S., Gill, T. M. 2016; 64 (3): 501-509

    Abstract

    To evaluate the effect of structured physical activity on respiratory outcomes in community-dwelling elderly adults with mobility limitations.Multicenter, randomized trial of physical activity vs health education, with respiratory variables prespecified as tertiary outcomes over an intervention period of 24-42 months. Physical activity included walking (goal of 150 min/week) and strength, flexibility, and balance training. Health education included workshops on topics relevant to older adults and upper extremity stretching exercises.Lifestyle Interventions and Independence in Elders (LIFE) Study.Community-dwelling persons aged 70-89 with Short Physical Performance Battery scores less than 10 (N = 1,635).Dyspnea severity (defined as moderate to severe according to a Borg index >2 immediately after a 400-m walk), forced expiratory volume in 1 second (FEV1) (

    View details for DOI 10.1111/jgs.14013

    View details for PubMedID 27000324

  • Biomarkers of oxidative stress are associated with frailty: the Framingham Offspring Study. Age (Dordrecht, Netherlands) Liu, C. K., Lyass, A., Larson, M. G., Massaro, J. M., Wang, N., D'Agostino, R. B., Benjamin, E. J., Murabito, J. M. 2016; 38 (1): 1

    Abstract

    Cardiovascular disease and frailty frequently occur together. Both are associated with inflammation, which may be partially triggered by oxidative stress, especially in cardiovascular disease. We investigated whether inflammatory and oxidative stress biomarkers linked to cardiovascular disease were associated with frailty and the related outcome of gait speed. We report cross-sectional associations of biomarkers and frailty assessed at Framingham Offspring Study cycle eight. Participants ?60 years were eligible if they had information on frailty and at least one of the following: C-reactive protein, interleukin-6, tumor necrosis factor receptor 2, 8-epi-FGF? isoprostanes (isoprostanes), lipoprotein phospholipase A2 (LpPLA2) mass or activity, osteoprotegerin, intracellular adhesion molecule-1, monocyte chemoattractant protein-1 or P-selectin. Stepwise logistic models were utilized for frailty and stepwise linear models for gait speed. Covariates included age, sex, body mass index, smoking, and co-morbidities. Odds ratios (ORs) and slope estimates (B) are reported per standard deviation increase of loge-transformed biomarker. Of the 1919 participants, 142 (7 %) were frail. In a stepwise model, frailty odds increased with higher interleukin-6 (OR 1.90, 95 % CI 1.51, 2.38), isoprostanes (OR 1.46, 95 % CI 1.12, 1.92), and LpPLA2 mass (OR 1.29, 95 % CI 1.00, 1.65). Stepwise regression found that slower gait speeds were associated with interleukin-6 (B?=?-0.025 m/s, 95 % CI 0.04, -0.01), isoprostanes (B?=?-0.019, 95 % CI -0.03, -0.008), LpPLA2 mass (B?=?-0.016, 95 % CI -0.03, -0.004), and osteoprotegerin (B?=?-0.015, 95 % CI -0.03, -0.002, all p?

    View details for DOI 10.1007/s11357-015-9864-z

    View details for PubMedID 26695510

    View details for PubMedCentralID PMC5005887

  • Effect of a Long-Term Physical Activity Intervention on Resting Pulse Rate in Older Persons: Results from the Lifestyle Interventions and Independence for Elders Study. Journal of the American Geriatrics Society Ó Hartaigh, B., Lovato, L. C., Pahor, M., Buford, T. W., Dodson, J. A., Forman, D. E., Buman, M. P., Demons, J. L., Santanasto, A. J., Liu, C., Miller, M. E., McDermott, M. M., Gill, T. M. 2016; 64 (12): 2511?16

    Abstract

    To assess the utility of a long-term physical activity (PA) intervention for reducing resting pulse rate (RPR) in older persons.Community.Lifestyle Interventions and Independence for Elders Study.Individuals aged 70 to 89 (N = 1,635, 67.2% women) were randomized to a moderate-intensity PA intervention (n = 818) or a health education-based successful aging (SA) intervention (n = 817).RPR was recorded at baseline and 6, 18, and 30 months. Longitudinal changes in RPR of intervention groups were compared using a mixed-effects analysis of covariance model for repeated-measure outcomes, generating least squares means with standard errors (SEs) or 95% confidence intervals (CIs).Mean duration of the study was 2.6 years (median 2.7 years, interquartile range 2.3-3.1 years). The average effect of the PA intervention on RPR over the course of the study period was statistically significant but clinically small (average intervention difference = 0.84 beats/min; 95% CI = 0.17-1.51; Paverage = .01), with the most pronounced effect observed at 18 months (PA, 66.5 beats/min (SE 0.32 beats/min); SA, 67.8 beats/min (SE 0.32 beats/min); difference = 1.37 beats/min, 95% CI = 0.48-2.26 beats/min). The relationship became somewhat weaker and was not statistically significant at 30 months. There were no significant differences between several prespecified subgroups.A long-term moderate-intensity PA program was associated with a small and clinically insignificant slowing of RPR in older persons. Whether PA can deliver a beneficial reduction in RPR requires further examination in older adults.

    View details for DOI 10.1111/jgs.14380

    View details for PubMedID 27787876

    View details for PubMedCentralID PMC5173403

  • Sedentary time is associated with the metabolic syndrome in older adults with mobility limitations - The LIFE Study EXPERIMENTAL GERONTOLOGY Mankowski, R. T., Aubertin-Leheudre, M., Beavers, D. P., Botoseneanu, A., Buford, T. W., Church, T., Glynn, N. W., King, A. C., Liu, C., Manini, T. M., Marsh, A. P., McDermott, M., Nocera, J. R., Pahor, M., Strotmeyer, E. S., Anton, S. D. 2015; 70: 32-36

    Abstract

    Epidemiological and objective studies report an association between sedentary time and lower risk of the metabolic syndrome (MetS) and its risk factors in young and middle-age adults. To date, there is a lack of objective data on the association between sedentary time and MetS among older adults.The association between objectively measured sedentary time (accelerometry) with MetS and MetS components was examined in a large sample of older adults with mobility limitations (N=1198; mean age=78.7 ± 5.3 years) enrolled in the Lifestyle Interventions and Independence for Elders (LIFE) study. Participants were divided into tertiles according to percentage of daily sedentary time, and the relation between sedentary time with MetS and MetS components was examined after adjusting for age, sex, ethnicity, and BMI.Participants in the highest sedentary time tertile had significantly higher odds of MetS (OR=1.54) (95% CI 1.13 to 2.11) in comparison with participants in the lowest tertile (p=0.03). Participants in the highest sedentary time tertile had larger waist circumference (p=0.0001) and lower HDL-C (p=0.0003) than participants in the lowest sedentary time tertile.Sedentary time was strongly related to higher odds of MetS. These results, based on objectively measured sedentary time, suggest that sedentary time may represent an important risk factor for the development of MetS in older adults with high likelihood for disability.

    View details for DOI 10.1016/j.exger.2015.06.018

    View details for PubMedID 26130060

  • Effect of Structured Physical Activity on Sleep-Wake Behaviors in Sedentary Elderly Adults with Mobility Limitations. Journal of the American Geriatrics Society Vaz Fragoso, C. A., Miller, M. E., King, A. C., Kritchevsky, S. B., Liu, C. K., Myers, V. H., Nadkarni, N. K., Pahor, M., Spring, B. J., Gill, T. M. 2015; 63 (7): 1381-1390

    Abstract

    To evaluate the effect of structured physical activity on sleep-wake behaviors in sedentary community-dwelling elderly adults with mobility limitations.Multicenter, randomized trial of moderate-intensity physical activity versus health education, with sleep-wake behaviors prespecified as a tertiary outcome over a planned intervention period ranging from 24 to 30 months.Lifestyle Interventions and Independence for Elders Study.Community-dwelling persons aged 70 to 89 who were initially sedentary and had a Short Physical Performance Battery score less than 10 (N = 1,635).Sleep-wake behaviors were evaluated using the Insomnia Severity Index (ISI) (?8 defined insomnia), Epworth Sleepiness Scale (ESS) (?10 defined daytime drowsiness), and Pittsburgh Sleep Quality Index (PSQI) (>5 defined poor sleep quality) administered at baseline and 6, 18, and 30 months.The randomized groups were similar in terms of baseline demographic variables, including mean age (79) and sex (67% female). Structured physical activity resulted in a significantly lower likelihood of having poor sleep quality (adjusted odds ratios (aOR) for PSQI >5 = 0.80, 95% confidence interval (CI) = 0.68-0.94), including fewer new cases (aOR for PSQI >5 = 0.70, 95% CI = 0.54-0.89), than health education but not in resolution of prevalent cases (aOR for PSQI ?5 = 1.13, 95% CI = 0.90-1.43). No significant intervention effects were observed for the ISI or ESS.Structured physical activity resulted in a lower likelihood of developing poor sleep quality (PSQI >5) over the intervention period than health education but had no effect on prevalent cases of poor sleep quality or on sleep-wake behaviors evaluated using the ISI or ESS. These results suggest that the benefit of physical activity in this sample was preventive and limited to sleep-wake behaviors evaluated using the PSQI.

    View details for DOI 10.1111/jgs.13509

    View details for PubMedID 26115386

  • The Vitality, Independence, and Vigor in the Elderly 2 Study (VIVE2): Design and methods. Contemporary clinical trials Kirn, D. R., Koochek, A., Reid, K. F., von Berens, Å., Travison, T. G., Folta, S., Sacheck, J., Nelson, M., Liu, C., Phillips, E., Åberg, A. C., Nydahl, M., Gustafsson, T., Cederholm, T., Fielding, R. A. 2015; 43: 164?71

    Abstract

    Nutritional supplementation may potentiate the increase in skeletal muscle protein synthesis following exercise in healthy older individuals. Whether exercise and nutrition act synergistically to produce sustained changes in physical functioning and body composition has not been well studied, particularly in mobility-limited older adults.The VIVE2 study was a multi-center, randomized controlled trial, conducted in the United States and Sweden. This study was designed to compare the effects of a 6-month intervention with a once daily, experimental, 4 fl.oz. liquid nutritional supplement providing 150 kcal, whey protein (20 g), and vitamin D (800 IU) (Nestlé Health Science, Vevey, Switzerland), to a low calorie placebo drink (30 kcal, non-nutritive; identical format) when combined with group-based exercise in 150 community-dwelling, mobility-limited older adults. All participants participated in a structured exercise program (3 sessions/week for 6 months), which included aerobic, strength, flexibility, and balance exercises.The primary outcome was 6-month change in 400 m walk performance (m/s) between supplement and placebo groups. Secondary outcomes included 6 month change in: body composition, muscle cross-sectional area, leg strength, grip strength, stair climb time, quality of life, physical performance, mood/depressive symptoms and nutritional status. These outcomes were selected based on their applicability to the health and well-being of older adults.The results of this study will further define the role of nutritional supplementation on physical functioning and restoration of skeletal muscle mass in older adults. Additionally, these results will help refine the current physical activity and nutritional recommendations for mobility-limited older adults.

    View details for DOI 10.1016/j.cct.2015.06.001

    View details for PubMedID 26044464

  • Combined Reduced Forced Expiratory Volume in 1 Second (FEV1) and Peripheral Artery Disease in Sedentary Elders With Functional Limitations JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION Fragoso, C. A., Hsu, F., Brinkley, T., Church, T., Liu, C. K., Manini, T., Newman, A. B., Stafford, R. S., McDermott, M. M., Gill, T. M. 2014; 15 (9): 665-670

    Abstract

    Because they are potentially modifiable and may coexist, we evaluated the combined occurrence of a reduced forced expiratory volume in 1 second (FEV1) and peripheral artery disease (PAD), including its association with exertional symptoms, physical inactivity, and impaired mobility, in sedentary elders with functional limitations.Cross sectional.Lifestyle Interventions and Independence in Elder (LIFE) Study.A total of 1307 sedentary community-dwelling persons, mean age 78.9, with functional limitations (Short Physical Performance Battery [SPPB] <10).A reduced FEV1 was defined by a z-score less than -1.64 (

    View details for DOI 10.1016/j.jamda.2014.05.008

    View details for Web of Science ID 000341167700011

    View details for PubMedID 24973990

    View details for PubMedCentralID PMC4145029

  • Effect of Structured Physical Activity on Prevention of Major Mobility Disability in Older Adults The LIFE Study Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Pahor, M., Guralnik, J. M., Ambrosius, W. T., Blair, S., Bonds, D. E., Church, T. S., Espeland, M. A., Fielding, R. A., Gill, T. M., Groessl, E. J., King, A. C., Kritchevsky, S. B., Manini, T. M., McDermott, M. M., Miller, M. E., Newman, A. B., Rejeski, W. J., Sink, K. M., Williamson, J. D. 2014; 311 (23): 2387-2396

    Abstract

    In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability.To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability.The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban, and rural communities at 8 centers throughout the United States. We randomized a volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m.Participants were randomized to a structured, moderate-intensity physical activity program (n?=?818) conducted in a center (twice/wk) and at home (3-4 times/wk) that included aerobic, resistance, and flexibility training activities or to a health education program (n?=?817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises.The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m.Incident major mobility disability occurred in 30.1% (246 participants) of the physical activity group and 35.5% (290 participants) of the health education group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98], P?=?.03).Persistent mobility disability was experienced by 120 participants (14.7%) in the physical activity group and 162 participants (19.8%) in the health education group (HR, 0.72 [95% CI, 0.57-0.91]; P?=?.006). Serious adverse events were reported by 404 participants (49.4%) in the physical activity group and 373 participants (45.7%) in the health education group (risk ratio, 1.08 [95% CI, 0.98-1.20]).A structured, moderate-intensity physical activity program compared with a health education program reduced major mobility disability over 2.6 years among older adults at risk for disability. These findings suggest mobility benefit from such a program in vulnerable older adults.clinicaltrials.gov Identifier: NCT01072500.

    View details for DOI 10.1001/jama.2014.5616

    View details for Web of Science ID 000337301500019

  • Respiratory Impairment and Dyspnea and Their Associations with Physical Inactivity and Mobility in Sedentary Community-Dwelling Older Persons JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Fragoso, C. A., Beavers, D. P., Hankinson, J. L., Flynn, G., Berra, K., Kritchevsky, S. B., Liu, C. K., McDermott, M., Manini, T. M., Rejeski, W. J., Gill, T. M. 2014; 62 (4): 622-628

    Abstract

    To evaluate the prevalence of respiratory impairment and dyspnea and their associations with objectively measured physical inactivity and performance-based mobility in sedentary older persons.Cross-sectional.Lifestyle Interventions and Independence for Elders Study.Community-dwelling older persons (n = 1,635, mean age 78.9) who reported being sedentary (<20 min/wk of regular physical activity and <125 min/wk of moderate physical activity in past month).Respiratory impairment was defined as low ventilatory capacity (forced expiratory volume in 1 second less than lower limit of normal (LLN)) and respiratory muscle weakness (maximal inspiratory pressure

    View details for DOI 10.1111/jgs.12738

    View details for Web of Science ID 000334289900004

    View details for PubMedCentralID PMC3989438

  • The impact of sarcopenia on a physical activity intervention: the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). The journal of nutrition, health & aging Liu, C. K., Leng, X., Hsu, F. C., Kritchevsky, S. B., Ding, J., Earnest, C. P., Ferrucci, L., Goodpaster, B. H., Guralnik, J. M., Lenchik, L., Pahor, M., Fielding, R. A. 2014; 18 (1): 59?64

    Abstract

    To determine if sarcopenia modulates the response to a physical activity intervention in functionally limited older adults.Secondary analysis of a randomized controlled trial.Three academic centers.Elders aged 70 to 89 years at risk for mobility disability who underwent dual-energy x-ray absorptiometry (DXA) for body composition at enrollment and follow-up at twelve months (N = 177).Subjects participated in a physical activity program (PA) featuring aerobic, strength, balance, and flexibility training, or a successful aging (SA) educational program about healthy aging.Sarcopenia as determined by measuring appendicular lean mass and adjusting for height and total body fat mass (residuals method), Short Physical Performance Battery score (SPPB), and gait speed determined on 400 meter course.At twelve months, sarcopenic and non-sarcopenic subjects in PA tended to have higher mean SPPB scores (8.7±0.5 and 8.7±0.2 points) compared to sarcopenic and non-sarcopenic subjects in SA (8.3±0.5 and 8.4±0.2 points, p = 0.24 and 0.10), although the differences were not statistically significant. At twelve months, faster mean gait speeds were observed in PA: 0.93±0.4 and 0.95±0.03 meters/second in sarcopenic and non-sarcopenic PA subjects, and 0.89±0.4 and 0.91±0.03 meters/second in sarcopenic and non-sarcopenic SA subjects (p = 0.98 and 0.26), although not statistically significant. There was no difference between the sarcopenic and non-sarcopenic groups in intervention adherence or number of adverse events.These data suggest that older adults with sarcopenia, who represent a vulnerable segment of the elder population, are capable of improvements in physical performance after a physical activity intervention.

    View details for DOI 10.1007/s12603-013-0369-0

    View details for PubMedID 24402391

    View details for PubMedCentralID PMC4111145

  • Chronic kidney disease defined by cystatin C predicts mobility disability and changes in gait speed: the Framingham Offspring Study. The journals of gerontology. Series A, Biological sciences and medical sciences Liu, C. K., Lyass, A., Massaro, J. M., D'Agostino, R. B., Fox, C. S., Murabito, J. M. 2014; 69 (3): 301?7

    Abstract

    As creatinine-based estimates of renal function are inaccurate in older adults, an alternative is an estimated glomerular filtration rate (eGFR(cys)) based on cystatin C. We examined the prospective association between chronic kidney disease (CKD(cys)) as determined by eGFR(cys) with the primary outcome of incident mobility disability and the secondary outcome of change in gait speed.Framingham Offspring Study participants older than 60 years and free of mobility disability at baseline (1998-2001) were eligible. Baseline CKD(cys) was defined as eGFR(cys) less than 60 mL/min/1.73 m(2). At follow-up (2005-2008), the outcomes of mobility disability, defined as self-reported inability to walk 1/2 mile and/or climb a flight of stairs, and gait speed were measured. Logistic and linear regression models were adjusted for age, sex, body mass index, smoking, diabetes, C reactive protein, and physical activity.Of 1,226 participants, 230 (19%) had CKD(cys) at baseline. After a mean follow-up of 6.6 years, 185 (15%) developed mobility disability. Of those with CKD(cys), 60 (26%) developed mobility disability. Those with CKD(cys) had greater odds of mobility disability in the age- and sex-adjusted (odds ratio [OR] 1.91, 95% CI 1.32, 2.75) and fully adjusted (OR 1.55, 95% CI 1.05, 2.31) models compared with those without CKD(cys). In fully adjusted models, participants with CKD(cys) had greater gait speed declines than those without CKD(cys) (? = 0.07 [SE 0.02], p = .0022).CKD(cys) was associated with higher odds of incident mobility disability and greater decline in gait speed, highlighting the loss of physical independence in elders with CKD.

    View details for DOI 10.1093/gerona/glt096

    View details for PubMedID 23913929

    View details for PubMedCentralID PMC3976137

  • JC virus binds to primary human glial cells, tonsillar stromal cells, and B-lymphocytes, but not to T lymphocytes. Journal of neurovirology Wei, G., Liu, C. K., Atwood, W. J. 2000; 6 (2): 127?36

    Abstract

    The human polyomavirus, JCV, is the etiological agent of the fatal central nervous system demyelinating disease, progressive multifocal leukoencephalopathy (PML). In PML patients, JC Virus (JCV) can be detected in glial cells in the central nervous system (CNS); in B-lymphocytes in the peripheral blood, bone marrow, spleen, and tonsil; and in tonsillar stromal cells. In vitro, JCV infects glial cells, tonsillar stromal cells, and to a limited extent B-lymphocytes. The presence or absence of as yet unidentified cell type specific transcription factors contributes to the restricted tropism of JCV for these cell types. However, several studies indicate that cell surface receptors may also contribute to the limited host range of JCV. To examine this latter possibility we measured the binding of purified JCV virions to primary cultures of glial cells, tonsillar stromal cells, peripheral blood lymphocytes, and to several established cell lines. Our results demonstrate that JCV binds to primary glial cells, stromal cells, and B cells, but does not bind to primary T cells. In contrast, JCV bound to all cell lines tested, including the Namalwa B cell line and the Jurkat T cell line. These data are novel and demonstrate that JCV selectively interacts with cells in vivo that are known to be susceptible to infection. This selectivity appears to be lost when one examines virus binding to a variety of human, monkey, or mouse tumor cell lines. We next examined the susceptibility of primary peripheral blood lymphocytes and the Namalwa B cell line to infection with JCV. Our results demonstrate that the majority of infectious JCV virions remain cell surface associated and do not efficiently establish infection of B cells. This may explain the in vivo observation that JCV DNA is frequently detected in association with lymphocytes by PCR but that JCV mRNA is rarely detected in association with lymphocytes by reverse transcriptase PCR. These results also confirm previous data regarding the association of JCV with human B cells in vivo and support the hypothesis that B cells may be involved in trafficking of JCV to the CNS.

    View details for DOI 10.3109/13550280009013156

    View details for PubMedID 10822326

  • The human polyomavirus, JCV, does not share receptor specificity with SV40 on human glial cells. Journal of neurovirology Liu, C. K., Hope, A. P., Atwood, W. J. 1998; 4 (1): 49?58

    Abstract

    The initial event in the life cycle of a virus is its interaction with specific receptors present on the surface of a cell. Understanding these interactions is important to our understanding of viral tropism and tissue specific pathology associated with viral disease. The human polyomavirus, JCV, is the etiological agent of the fatal central nervous system (CNS) demyelinating disease, progressive multifocal leukoencephalopathy (PML). PML is the direct result of JCV infection of oligodendrocytes, the myelin producing cell in the CNS. In vivo, JCV can be detected in oligodendrocytes, astrocytes, lymphoid tissue, and peripheral blood of PML patients. In vitro, JCV infects human glial cells, tonsilar stromal cells, and, to a limited extent, human B lymphocytes. The initial step in infection of cells by JCV is at the level of attachment and entry. A specific cell surface receptor for JCV on human glial cells has not been identified. To begin to understand the nature of JCV receptors on human glial cells, large quantities of a previously characterized hybrid JC virus (Mad-1/SVEdelta) were purified. A direct virus binding assay demonstrated that these highly purified and labeled JCV virions bound to a finite number of cellular receptors on human glial cells. A competitive virus binding assay demonstrated that an excess of unlabeled JCV competed with labeled JCV more efficiently than did an excess of purified SV40. Furthermore, anti-class I antibodies which inhibited infection of glial cells by SV40 had no significant effect on infection by JCV. These results imply that JCV does not share receptor specificity with the related polyomavirus, SV40.

    View details for DOI 10.3109/13550289809113481

    View details for PubMedID 9531011

  • Infection of glial cells by the human polyomavirus JC is mediated by an N-linked glycoprotein containing terminal alpha(2-6)-linked sialic acids. Journal of virology Liu, C. K., Wei, G., Atwood, W. J. 1998; 72 (6): 4643?49

    Abstract

    The human JC polyomavirus (JCV) is the etiologic agent of the fatal central nervous system (CNS) demyelinating disease progressive multifocal leukoencephalopathy (PML). PML typically occurs in immunosuppressed patients and is the direct result of JCV infection of oligodendrocytes. The initial event in infection of cells by JCV is attachment of the virus to receptors present on the surface of a susceptible cell. Our laboratory has been studying this critical event in the life cycle of JCV, and we have found that JCV binds to a limited number of cell surface receptors on human glial cells that are not shared by the related polyomavirus simian virus 40 (C. K. Liu, A. P. Hope, and W. J. Atwood, J. Neurovirol. 4:49-58, 1998). To further characterize specific JCV receptors on human glial cells, we tested specific neuraminidases, proteases, and phospholipases for the ability to inhibit JCV binding to and infection of glial cells. Several of the enzymes tested were capable of inhibiting virus binding to cells, but only neuraminidase was capable of inhibiting infection. The ability of neuraminidase to inhibit infection correlated with its ability to remove both alpha(2-3)- and alpha(2-6)-linked sialic acids from glial cells. A recombinant neuraminidase that specifically removes the alpha(2-3) linkage of sialic acid had no effect on virus binding or infection. A competition assay between virus and sialic acid-specific lectins that recognize either the alpha(2-3) or the alpha(2-6) linkage revealed that JCV preferentially interacts with alpha(2-6)-linked sialic acids on glial cells. Treatment of glial cells with tunicamycin, but not with benzyl N-acetyl-alpha-D-galactosaminide, inhibited infection by JCV, indicating that the sialylated JCV receptor is an N-linked glycoprotein. As sialic acid containing glycoproteins play a fundamental role in mediating many virus-cell and cell-cell recognition processes, it will be of interest to determine what role these receptors play in the pathogenesis of PML.

    View details for DOI 10.1128/JVI.72.6.4643-4649.1998

    View details for PubMedID 9573227

    View details for PubMedCentralID PMC109982

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