Jesse Poganik, Codirector, Biomarkers of Aging Consortium, on the hurdles and promise of bringing aging biomarkers to the clinic.
The promise of aging biomarkers has never been more compelling. With a single blood sample, we can now estimate not just how many years someone has lived, but how well their body has weathered those years. Biomarkers built from proteins, DNA methylation patterns, and other modalities represent one of the most exciting frontiers in aging research. However, these tools largely remain confined to research laboratories, unable to fulfill their remarkable clinical potential. The gap between their proven ability to predict age-related risks in cohort studies and their application in real-world medicine reveals fundamental questions about how these biomarkers perform in clinical contexts that we have not yet sufficiently answered.
The dynamics we don’t understand
Perhaps the most critical missing piece is understanding how biological age measurements change over time within individuals. With some notable exceptions, current aging biomarkers are largely built from cross-sectional studies that capture single molecular snapshots from many individuals. These models can suggest that a 50-year-old with the biological profile of an average 60-year-old may face elevated health risks, but cannot reveal whether that measurement represents a temporary spike due to recent illness, a chronic elevation requiring intervention, or natural variation within normal limits. Without understanding the range and determinants of natural fluctuations in biological age, clinicians cannot properly interpret results or distinguish meaningful changes from normal variation, seriously hindering the actionability of these biomarkers.
Recent research has begun revealing that fluctuations in biological age predictions can be associated with factors like major physiological stress and intense exercise. These findings suggest that aging biomarkers capture something more dynamic than previously appreciated, but the clinical significance of these fluctuations remains largely unknown. For instance, do temporary elevations in biological age predict poor recovery from surgery? Do they indicate when someone might benefit from additional medical monitoring? These types of questions cannot be answered without longitudinal studies that carefully track the same individuals over time.
The response problem
Equally critical is understanding how aging biomarkers respond to interventions. A key goal of implementing biomarkers of aging in the clinic is to guide decisions about treatments, lifestyle changes, or preventive measures that could extend healthy lifespan. Yet most aging biomarkers have not yet been tested for their ability to detect improvements from geroprotective interventions.
This creates a circular problem: we cannot easily test interventions that target aging without reliable biomarkers that respond to beneficial changes, but we cannot validate the response properties of biomarkers without interventions of known efficacy. Breaking this cycle requires studies that simultaneously test interventions and track biomarker responses, linking molecular changes to hard clinical outcomes like intrinsic capacity, disease incidence, and quality of life.
Technical and practical barriers
Beyond these conceptual challenges, practical barriers limit clinical adoption. Many promising aging biomarkers require expensive omics-profiling assays or specialized expertise that puts them out of reach for routine clinical use. Many such assays cost hundreds of dollars per sample. Cost considerations become even more critical when considering that aging biomarkers would ideally be applied broadly for risk stratification and prevention in generally healthy populations. This application necessitates tests that are not only reliable and actionable but also affordable and accessible. Affordability will also enable the needed longitudinal studies mentioned above.
Data sharing represents another persistent obstacle. Robust validation of aging biomarkers across populations requires multiple large datasets, but researchers often struggle to access such data. Without this validation, performance of biomarkers across populations remains unclear, and regulatory agencies and clinicians will likely remain skeptical about adopting aging biomarkers for clinical decision making.
Promising developments on the horizon
Despite these challenges, major new initiatives are positioned to address critical knowledge gaps in aging biomarker research. The XPRIZE Healthspan competition represents a particularly promising development for understanding biomarker response properties. By collecting biological samples before and after healthspan-targeting interventions, this competition stands to generate precisely the type of data needed to link biomarker changes with hard outcomes in muscle, cognitive, and immune function. This design has the potential to provide unprecedented insights into which aging biomarkers best capture meaningful health improvements, setting the stage for prioritization of biomarkers as surrogate endpoints for future healthspan trials.
Similarly, the Advanced Research Projects Agency for Health’s PROSPR initiative promises to tackle multiple biomarker challenges simultaneously. This program aims to develop an intrinsic capacity score and understand both its longitudinal behavior and response properties. By taking a systematic approach to biomarker development and validation, PROSPR could establish the evidence base needed for regulatory approval of aging biomarkers as clinical tools and validated surrogate endpoints.
The path forward
These initiatives represent an exciting new chapter for the field, moving beyond discovery and proof-of-concept studies. The next phase of aging biomarker research must prioritize longitudinal studies that track individuals over time, intervention studies that test biomarker responsiveness, and validation efforts that establish clinical utility across populations. Success will require collaboration between biomarker developers, clinicians, regulatory agencies, and biotech companies. The rapid growth of the Biomarkers of Aging Consortium signals shared enthusiasm across these sectors to work together to achieve our common goals.
The potential rewards justify such an extensive undertaking. Aging biomarkers that successfully translate to the clinic could transform healthcare from reactive disease treatment to proactive health preservation. Such tools could guide personalized interventions, optimize treatment timing, and help individuals make informed decisions about their health. As major new initiatives like XPRIZE Healthspan and PROSPR begin generating critical data, it will be exciting to see what other efforts emerge to accelerate the journey of aging biomarkers from proven research tools to useful clinical tests. Critical missing pieces are now poised to be addressed, bringing us closer to a future where measuring biological age becomes as routine as checking blood pressure or cholesterol levels.
About Jesse Poganik 
Dr Jesse Poganik is an Investigator at Brigham and Women’s Hospital and Instructor in Medicine at Harvard Medical School. His research focuses on understanding the most fundamental aspects of aging and leveraging this knowledge to identify the most efficient ways to extend healthy lifespan. Dr Poganik also co-directs Biomarkers of Aging Consortium that works to bring aging biomarkers to clinical applications.