With the uptick of research to assess and better understand the accumulation of molecular and cellular damage over time related to human aging, a new study from researchers at the Brigham and Women’s Hospital has proposed a standardized framework for the validation of these emerging biomarkers. Such a framework could help speed adoption of translating this knowledge into the clinic for both precision treatments and preventative care, the team contends in their recent work published in Nature Medicine.
To test the concept, the Brigham and Women’s investigators examined data from population-based cohort studies of known blood-based biomarkers of aging using multi-omic datasets. Armed with these data, the researchers sought to identify what the challenges might be in determining the relative impact of different biomarkers, such as variations in study design and data collection, as well as the variation of the diversity of populations from the different data.
“If we hope to have clinical trials for interventions that extend healthy lifespan in humans, we need reliable, validated biomarkers of aging,” said co-first author Jesse Poganik, PhD, of the division of genetics at Brigham and Women’s. “We hope that our framework will help prioritize the most promising biomarkers and provide health care providers with clinically valuable and actionable tools.”
Based on their findings, the researchers provided recommendations on how to address the challenges of working with diverse datasets from different biomarker studies of aging. Among their recommendations:
- Adopting “multi-omic approaches” involving a breadth of technologies like metabolomics, proteomics and epigenetics, and transcriptomics to provide greater insights into biomarker predictive performance.
- Shift the assessment of mortality as an age-related outcome to consider biomarker associations with other health factors such as functional decline, frailty, chronic diseases, and disability.
- A standardization of omic data to enhance biomarker validation efforts. “Omics and biomarkers harmonization efforts, such as the Bio-learn project, are instrumental in validation of biomarkers of aging” said co-first author Mahdi Moqri, PhD, of the division of genetics.
The proposed framework also encourages closer and increased collaboration between research groups on large-scale, longitudinal studies in order to track physiological changes of people over time and better understand the response of people in diverse populations to therapeutic interventions. This would also help inform how using biomarker evaluations in clinical trials can help inform improving both quality of life and survival for patients.
“Such biomarkers could predict aging-related outcomes and could serve as surrogate endpoints for the evaluation of interventions promoting healthy aging and longevity,” the researchers wrote. “However, no consensus exists on how biomarkers of aging should be validated before their translation to the clinic.”
