ORCID Profile
0000-0002-7797-8571
Current Organisation
University of Southampton
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Frontiers Media SA
Date: 10-09-2019
Publisher: Springer Science and Business Media LLC
Date: 04-10-2023
Publisher: Elsevier BV
Date: 03-2023
Publisher: Springer Science and Business Media LLC
Date: 08-01-2019
Publisher: Elsevier BV
Date: 05-2017
Publisher: Springer Science and Business Media LLC
Date: 20-12-2019
DOI: 10.1038/S41467-019-13694-1
Abstract: The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. In iduals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD + levels through perturbed NAD + biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.
Publisher: Wiley
Date: 15-06-2021
DOI: 10.1002/RCO2.44
Abstract: Despite increasing knowledge of the pathogenesis of muscle ageing, the molecular mechanisms are poorly understood. Based on an expression analysis of muscle biopsies from older Caucasian men, we undertook an in‐depth analysis of the expression of the long non‐coding RNA, H19 , to identify molecular mechanisms that may contribute to the loss of muscle mass with age. We carried out transcriptome analysis of vastus lateralis muscle biopsies from 40 healthy Caucasian men aged 68–76 years from the Hertfordshire Sarcopenia Study (HSS) with respect to appendicular lean mass adjusted for height (ALMi). Validation and replication was carried out using qRT‐PCR in 130 independent male and female participants aged 73–83 years recruited into an extension of the HSS (HSSe). DNA methylation was assessed using pyrosequencing. Lower ALMi was associated with higher muscle H19 expression ( r 2 = 0.177, P 0.001). The microRNAs, miR‐675‐5p/3p encoded by exon 1 of H19 , were positively correlated with H19 expression (Pearson r = 0.192 and 0.182, respectively, P 0.03), and miR‐675‐5p expression negatively associated with ALMi ( r 2 = 0.629, P = 0.005). The methylation of CpGs within the H19 imprinting control region (ICR) were negatively correlated with H19 expression (Pearson r = −0.211 to −0.245, P ≤ 0.05). Moreover, RNA and protein levels of SMAD1 and 5 , targets of miR‐675‐3p , were negatively associated with miR‐675‐3p ( r 2 = 0.792 and 0.760, respectively) and miR‐675‐5p ( r 2 = 0.584 and 0.723, respectively) expression, and SMAD1 and 5 RNA levels positively associated with greater type II fibre size ( r 2 = 0.184 and 0.246, respectively, P 0.05). Increased expression profiles of H19/miR‐675‐5p/3p and lower expression of the anabolic SMAD1/5 effectors of bone morphogenetic protein (BMP) signalling are associated with low muscle mass in older in iduals.
Publisher: Elsevier BV
Date: 06-2021
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Philip Titcombe.