Biomarkers of Healthy and Pathological Aging: From Intrinsic Capacity to Frailty Syndromes

Aging of the musculoskeletal system is a major driver of functional decline, loss of independence, and frailty. Changes in muscle, bone, joints, and connective tissues underpin impairments in strength, balance, and mobility, and contribute to sarcopenia, osteoporosis, osteoarthritis, falls, and fractures. Chronological age alone does not capture this complexity. Frameworks such as intrinsic capacity (IC)—particularly its locomotor domain—and frailty syndromes offer a functional lens to understand how musculoskeletal aging shapes trajectories from robustness to vulnerability.

There is a growing need for biomarkers that characterize healthy and pathological musculoskeletal aging across this continuum, from preserved locomotor intrinsic capacity to sarcopenia, mobility limitation, and musculoskeletal frailty. Such biomarkers can deepen our understanding of mechanisms, enable early detection of high-risk states, and guide interventions aimed at preserving mobility, preventing disability, and reducing fall and fracture risk. Research in this area spans molecular and cellular changes, structural and functional imaging, performance-based assessments, and digital measures of mobility, but these strands are often studied in isolation.

This Research Topic aims to advance the identification, validation, and application of biomarkers of musculoskeletal aging that capture transitions along the intrinsic capacity–frailty spectrum. We particularly welcome work that links biological processes in muscle, bone, and joints to clinical outcomes and explores how biomarker information can inform prevention and personalized care in older adults.

We encourage submissions addressing, but not limited to, the following areas:

Molecular and cellular biomarkers of musculoskeletal aging, including inflammatory and metabolic markers, myokines, bone turnover markers, cartilage and connective tissue biomarkers, genomic and epigenetic signatures, mitochondrial dysfunction, and neuromuscular changes relevant to sarcopenia, osteoporosis, and frailty.

Physiological, functional, and imaging biomarkers of locomotor intrinsic capacity, such as gait speed, balance, strength and power, mobility tests, fall and fracture risk indices, and imaging of muscle (e.g., DXA, CT, MRI, ultrasound), bone (e.g., BMD, microarchitecture), and joints (e.g., radiographic or MRI osteoarthritis) across stages of musculoskeletal aging.

Digital and real-world mobility biomarkers, derived from wearables, smartphones, and ambient sensors, including walking patterns, activity levels, sedentary time, gait quality and variability, and falls, as well as approaches using artificial intelligence or machine learning to integrate multimodal data and predict mobility decline and musculoskeletal frailty.

Population and context-specific biomarker profiles, examining how sex, gender, ethnicity, lifestyle, comorbidities, and treatments influence musculoskeletal aging trajectories, and how biomarkers perform across clinical, rehabilitation, and community settings.

Prognostic and interventional applications, including prediction of functional decline, disability, fractures, hospitalization, institutionalization, and mortality, and the use of biomarkers as endpoints or stratification tools in exercise, nutritional, pharmacological, surgical, and rehabilitation interventions targeting musculoskeletal health, intrinsic capacity, and frailty.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Intrinsic capacity, Musculoskeletal aging, Frailty syndromes, Biomarkers, Sarcopenia

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.