Developing a toolkit for the assessment and monitoring of musculoskeletal ageing.

Graham J Kemp ,Silvia Del Din,Daniel J Cuthbertson,Giuseppe De Vito,Claudia Mazzà,Matthias Hackl,Richard Eastell,Richard Hodgson,Anne Mcardle,Stefano Schiaffino,Sue Lord,Patrick Garnero,Fraser Birrell,Jaap H Van Dieën ,Katarzyna Goljanek‐Whysall ,Malcolm J Jackson ,Peter Clegg ,Marco V Narici ,Mandy J Peffers ,Eugène Mccloskey ,John C Mathers

doi:10.1093/ageing/afy143

Abstract

The complexities and heterogeneity of the ageing process have slowed the development of consensus on appropriate biomarkers of healthy ageing. The Medical Research Council–Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between researchers and clinicians at the Universities of Liverpool, Sheffield and Newcastle. One of CIMA’s objectives is to ‘Identify and share optimal techniques and approaches to monitor age-related changes in all musculoskeletal tissues, and to provide an integrated assessment of musculoskeletal function’—in other words to develop a toolkit for assessing musculoskeletal ageing. This toolkit is envisaged as an instrument that can be used to characterise and quantify musculoskeletal function during ‘normal’ ageing, lend itself to use in large-scale, internationally important cohorts, and provide a set of biomarker outcome measures for epidemiological and intervention studies designed to enhance healthy musculoskeletal ageing. Such potential biomarkers include: biochemical measurements in biofluids or tissue samples, in vivo measurements of body composition, imaging of structural and physical properties, and functional tests. This review assesses candidate biomarkers of musculoskeletal ageing under these four headings, details their biological bases, strengths and limitations, and makes practical recommendations for their use. In addition, we identify gaps in the evidence base and priorities for further research on biomarkers of musculoskeletal ageing.

Highlights

Despite the limited consensus on biomarkers of ageing, Butler and colleagues have usefully defined three criteria for such markers [3]: the biomarker should predict the outcome of a wide range of age-sensitive tests in multiple physiological and behavioural domains, in an age-coherent way, and do so better than chronological age; it should predict remaining longevity at an age at which 90% of the population is still alive, and do so for most of the specific illnesses that afflict the species under study; and its measurement should not alter life expectancy or the outcome of subsequent age-sensitive tests
Workshop participants were tasked with defining a framework for the selection of biomarkers of ageing that are relevant to the multiple tissues of the musculoskeletal system, are distinct from markers of disease, change with age and are sensitive to intervention
We have reviewed potential biomarkers of musculoskeletal ageing, and the key biological and technical issues that bear on their inclusion or otherwise in a Centre for Integrated research into Musculoskeletal Ageing (CIMA) toolkit

Summary

Introduction

Ageing is associated with the accumulation of damage to all the macromolecules within and outside cells leading to progressively more cellular and tissue defects and resulting in age-related frailty, disability and disease [1]. The ambitions for the toolkit are that it should: characterise and quantify musculoskeletal function over multiple decades, i.e. during ‘normal’ ageing; facilitate epidemiological assessment of musculoskeletal decline, provide a set of outcome measures for intervention studies (using, e.g. drugs or lifestyle) designed to enhance healthy musculoskeletal ageing and become the protocol of choice, adopted by multiple large-scale, internationally important cohorts. Workshop participants were tasked with defining a framework for the selection of biomarkers of ageing that are relevant to the multiple tissues of the musculoskeletal system, are distinct from markers of disease, change with age and are sensitive to intervention. Recognising that research on biomarkers relevant to specific musculoskeletal tissues and biomarkers of different types is not all at the same stage of development and validation, workshop participants were asked to distinguish between immediately useful biomarkers and those of the generation when making recommendations for the proposed toolkit.

Aims and structure of this report

Key points

Findings

Conflict of interest