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11. Novel microRNA regulation of skeletal and cardiac muscle mass in chronic disease

Author

Connolly, Martin, Kemp, Paul, and Wort, Stephen

Subjects
610
Abstract

Skeletal muscle is a major tissue in the body, and, as a consequence of chronic illness or ageing, can be lost in a process known as wasting or atrophy. Muscle wasting individuals have a worse quality of life and increased mortality. The molecular mechanisms responsible for the reduction in mass are not well understood. MicroRNAs (miRNAs) are small non-coding RNAs that reduce mRNA half-life and translation. Previous work by the group identified miR-424-5p and miR-1-5p as being up-regulated and down-regulated, respectively, in a cohort of patients with chronic obstructive pulmonary disease (COPD). In this thesis, the expression of miR-424-5p was determined in cohorts of individuals who are sarcopenic and those with intensive care unit-acquired weakness (ICUAW), and found to be up-regulated compared to controls. miR-424-5p associated negatively with measures of disease severity in all cohorts, and muscle mass and function in COPD. In vitro studies revealed miR-424-5p inhibited the expression of components required to transcribe ribosomal RNA (rRNA), and reduced maximal translational capacity. Targeting of insulin-like growth factor 1 (IGF-1) by miR-424-5p was also confirmed. In vivo, overexpression of this miRNA caused atrophy in tibialis anterior (TA) muscles of mice and downregulation of mature rRNAs, suggesting that miRNA induced ribosomal stress may contribute to the atrophy. miR-424-5p expression was down-regulated in the hypertrophied right ventricle (RV) of rats with pulmonary arterial hypertension (PAH), while IGF-1 protein and rRNA was up-regulated, suggesting targets of this miRNA may promote hypertrophy following miR-424-5p downregulation. Additionally, miR-1-5p was shown to target TGF-βR1 (alk5), and these components were down-regulated and up-regulated respectively in the RV of PAH rats, suggesting another mechanism of hypertrophy propagation. Together, these data present novel mechanisms through which skeletal and cardiac muscle mass may be regulated in chronic disease and ageing.

Published
2018
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21. The Cluster-Randomized BRIGHT Trial: Proactive Case Finding for Community-Dwelling Older Adults

Author

Kerse, Ngaire, McLean, Chris, Moyes, Simon A, Peri, Kathy, Ng, Terence, Wilkinson-Meyers, Laura, Brown, Paul, Latham, Nancy, and Connolly, Martin

Subjects
Biomedical and Clinical Sciences, Health Services and Systems, Health Sciences, Clinical Sciences, Human Society, Social Work, Clinical Trials and Supportive Activities, Health Services, Comparative Effectiveness Research, Clinical Research, Rehabilitation, Aging, Aged, Aged, 80 and over, Disability Evaluation, Female, Geriatric Assessment, Health Status, Homes for the Aged, Hospitalization, Humans, Independent Living, Interviews as Topic, Male, Quality of Life, disability, early medical intervention, older adults, population screening, practice-based research, primary care, Medical and Health Sciences, Studies in Human Society, General & Internal Medicine, Biomedical and clinical sciences, Health sciences, Human society
Abstract

PurposePeople are now living longer, but disability may affect the quality of those additional years of life. We undertook a trial to assess whether case finding reduces disability among older primary care patients.MethodsWe conducted a cluster-randomized trial of the Brief Risk Identification Geriatric Health Tool (BRIGHT) among 60 primary care practices in New Zealand, assigning them to an intervention or control group. Intervention practices sent a BRIGHT screening tool to older adults every birthday; those with a score of 3 or higher were referred to regional geriatric services for assessment and, if needed, service provision. Control practices provided usual care. Main outcomes, assessed in blinded fashion, were residential care placement and hospitalization, and secondary outcomes were disability, assessed with Nottingham Extended Activities of Daily Living Scale (NEADL), and quality of life, assessed with the World Health Organization Quality of Life scale, abbreviated version (WHOQOL-BREF).ResultsAll 8,308 community-dwelling patients aged 75 years and older were approached; 3,893 (47%) participated, of whom 3,010 (77%) completed the trial. Their mean age was 80.3 (SD 4.5) years, and 55% were women. Overall, 88% of the intervention group returned a BRIGHT tool; 549 patients were referred. After 36 months, patients in the intervention group were more likely than those in the control group to have been placed in residential care: 8.4% vs 6.2% (hazard ratio = 1.32; 95% CI, 1.04-1.68; P = .02). Intervention patients had smaller declines in mean scores for physical health-related quality of life (1.6 vs 2.9 points, P = .007) and psychological health-related quality of life (1.1 vs 2.4 points, P = .005). Hospitalization, disability, and use of services did not differ between groups, however.ConclusionsOur case-finding strategy was effective in increasing identification of older adults with disability, but there was little evidence of improved outcomes. Further research could trial stronger primary care integration strategies.

Published
2014

26. Care Homes

Author

Worrall, Richard, primary, Boyd, Michal, additional, Connolly, Martin, additional, and Balmer, Deborah, additional

Published
2019
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30. Additional file 1 of Atrial fibrillation incidence and outcomes in two cohorts of octogenarians: LiLACS NZ

Author

Teh, Ruth, Kerse, Ngaire, Pillai, Avinesh, Lumley, Thomas, Rolleston, Anna, Kyaw, Tin Aung, Connolly, Martin, Broad, Joanna, Monteiro, Elaine, Clair, Valerie Wright-St, and Doughty, Robert N.

Abstract

Additional file 1: STable 1. number of participants prescribed with anticoagulant over 5 years follow-up. STable 2a. Multivariate Cox regression analysis for 5-year new stroke outcome in octogenarians (excluding recurrent stroke). STable 2b. Multivariate Cox regression analysis for 5-year new stroke outcome in octogenarians (excluding recurrent stroke). STable 3a. Multivariate Cox regression analysis for 5-year mortality of octogenarians. STable 3b. Multivariate Cox regression analysis for 5-year mortality of octogenarians.

Published
2023
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47. Prevalence of Loneliness and Its Association With General and Health-Related Measures of Subjective Well-Being in a Longitudinal Bicultural Cohort of Older Adults in Advanced Age Living in New Zealand: LiLACS NZ

Author

Lay-Yee, Roy, primary, Milne, Barry J, additional, Wright-St Clair, Valerie A, additional, Broad, Joanna, additional, Wilkinson, Tim, additional, Connolly, Martin, additional, Teh, Ruth, additional, Hayman, Karen, additional, Muru-Lanning, Marama, additional, and Kerse, Ngaire, additional

Published
2022
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