Frailty Trajectories and Modifiable Determinants: From Biomarkers to Clinical Guidelines

Frailty is increasingly recognized as a dynamic, multifactorial syndrome that arises from cumulative declines in multiple physiological systems, resulting in increased vulnerability to stressors and adverse health outcomes. Traditionally viewed as a static condition, frailty is now understood to follow distinct trajectories—individuals may progress from robust health to pre-frailty and frailty, with some showing resilience or even recovery. However, the biological, clinical, and social factors that influence the pace, variability, and potential reversibility of these trajectories remain underexplored, particularly in aging and diverse clinical populations. As our populations age, mapping the progression of frailty and understanding its nuanced pathways are essential to designing interventions that promote healthy longevity, reduce disability, and optimize care delivery.

A growing body of research has begun to illuminate the complex interplay of factors that modulate frailty’s onset and progression. Chronic inflammation, immunosenescence, metabolic and mitochondrial dysfunction, and sarcopenia all play critical biological roles, while nutrition, physical activity, sleep, medication burden, mental health, and social connectedness emerge as key clinical and behavioral determinants. Environmental factors such as access to health care, socioeconomic status, and living environment further influence frailty risk and resilience. The integration of biomarker research—including genomics, proteomics, metabolomics, and digital health data—holds promise for improving the early detection and ongoing monitoring of frailty. However, translating these insights into actionable clinical guidelines remains a major challenge.

This Research Topic aims to accelerate the understanding of frailty trajectories and highlight modifiable determinants that can be targeted for early intervention. We welcome submissions that characterize longitudinal patterns of frailty, identify and validate novel biomarkers, explore predictive models, and examine the impact of behavioral, clinical, or environmental modifications. We seek both mechanistic and applied research—including intervention studies, implementation science, consensus statements, and clinical guidelines—that bridges the gap between bench discoveries and bedside practice. Our goal is to inform individual risk stratification, improve patient-centered care, and provide a robust evidence base for the development of guidelines that support healthy aging across diverse settings.

We encourage contributions from geriatrics, primary care, rehabilitation, nutrition, epidemiology, public health, and beyond. Submissions may include original research, reviews, meta-analyses, protocols, perspectives, as well as collaborative and multidisciplinary studies. By shedding light on modifiable drivers of frailty and aligning scientific progress with clinical practice, this collection aims to advance the field and positively impact aging populations worldwide.

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
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• ... 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
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Frailty, Trajectories, Modifiable determinants, Biomarkers, Clinical guidelines

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.