Brigham researchers offer cohesive framework for evaluating biomarkers of aging

New paper documents framework for the classification and evaluation of biomarkers of aging and lays groundwork for future longevity advances.

‘Aging’ can be a slippery concept as it can refer to different processes, making it tricky to pin down and define a single and highly generalizable molecule or method to measure aging processes. In turn, there are molecular, biological, functional, clinical and phenotypic biomarkers of aging that lack consistency.

Longevity.Technology: Researchers at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, which leads the Biomarkers of Aging Consortium, collaborated with experts in aging across the world to systematically adapt and extend existing frameworks to classify biomarkers of aging and their clinical applications. Jesse Poganik, Mahdi Moqri and Vadim Gladyshev are leaders at the Biomarkers of Aging Consortium and among the authors of a paper published in Cell today that provides valuable insights into the conceptual, technical, and scientific considerations surrounding biomarkers of aging.

“As insights into the fundamental biology of aging expand, our work provides a robust framework for the classification and evaluation of biomarkers while documenting challenges and future directions in the field,” said study author Jesse Poganik, PhD, of the Division of Genetics at the Brigham.

Dr Poganik told Longevity.Technology that the team worked closely with a group of leading scientists from academia and industry, clinicians and regulatory experts to survey biomarkers of aging and their application in clinical studies – and that there was a particular focus on their use in identifying and evaluating interventions to promote healthy longevity.

“We were able to achieve consensus on working terminology for key concepts such as aging and biological age, and a classification scheme for biomarkers of aging,” he explains. “With these critical foundations in place, we surveyed the current state of biomarkers of aging and the applications they have found in clinical trials. Our framework was developed to provide researchers with a list of criteria against which biomarkers of aging may be evaluated and covers issues such as feasibility, age-sensitivity, generalizability, and validation, among others. Finally, we lay out the most pressing challenges in the aging biomarkers space and directions for future work. We hope that this manuscript will serve as a useful reference document for developers and users of aging biomarkers and will provide a toolset to evaluate existing and novel biomarkers of aging.”

L-R: Vadim Gladyshev, Jesse Poganik and Mahdi Moqri, leaders at the Biomarkers of Aging Consortium

“Once validated across different populations and settings, advanced omic biomarkers will equip us with powerful tools to monitor healthy aging, screen for diseases of aging, and identify longevity interventions,” said study author Mahdi Moqri, PhD, also of the Division of Genetics.

When it came to evaluating the key biomarker criteria, Poganik told us that while there was a lot of conceptual ground to cover in this space, the authors tried to be as comprehensive as possible.

“The considerations run the gamut from straightforward technical aspects such as which biological material is collected for measurement, to more nuanced considerations such as the difference between measuring biological age versus the rate of aging. In all, we covered the following topics: feasibility and validity, age-sensitivity criteria, mechanistic criteria, generalizability criteria, response criteria, and cost considerations.”

Brigham researchers offer cohesive framework for evaluating biomarkers of aging
Relation between biomarkers of aging and geroprotectors
Biomarkers of aging and geroprotectors may appear to have a circular relationship (A). However, development of each is useful to the other: evaluated geroprotectors can be used to develop and benchmark biomarkers of aging, while evaluated biomarkers of aging may be used to predict or test the response to candidate geroprotectors (B)

The authors also reviewed processes to validate these biomarkers analytically, through reproducible lab measurements, and clinically, through outcomes observed in human research. Finally, they reviewed key challenges for biomarkers to be used clinically, such as differentiating those that assess chronological age from those used to measure rate of aging, offering a novel framework to prepare a biomarker to advance towards clinical use.

“The ability to quantify biological age and determine how it is affected by interventions is a major advance in the field,” said Vadim Gladyshev, Professor of Medicine, the corresponding author of the article. “It is also critical to define the terms at the heart of what we study, including aging, biological age, biomarker of aging, etc, which may lay the foundation for future advances.”

As mentioned, methods of measuring aging are myriad, so the authors’ undertaking to create their framework came with this challenge built in.

“This manuscript is our attempt to take the first steps to overcome this major challenge,” Jesse Poganik explained to Longevity.Technology.

“The reality is that there is likely no single correct answer on how to best measure aging. This is why we put together a framework to evaluate these tools, which are being continuously developed and released, rather than anointing particular biomarkers as the “best” tools for measuring aging. As you might guess from the fact that we wrote an entire manuscript on this topic, there are a huge number of conceptual, technical, and scientific considerations surrounding biomarkers of aging.

Poganik told us that a key achievement of this work is the establishment of a baseline of consensus on how these tools may be evaluated, and the authors hope the manuscript will become a useful reference and the framework a useful tool for researchers who are interested in the evaluation of biomarkers of aging and their eventual clinical use.

“We also hope that the consortium community will continue to work together towards achieving this goal through ongoing efforts such as our annual symposium, which will be held for the first time on December 4, 2023.”

So, what are the next steps in implementing this framework in practice?

“We have made significant efforts to connect diverse stakeholders who work on various aspects of biomarkers of aging, so we hope that the formation of the consortium itself will be a catalyst in propelling these tools forward to the clinic,” Jesse Poganik told Longevity.Technology.

“There is a long road to reaching that goal, though. One of the key outstanding challenges is systematic validation of aging biomarkers.” The team plan to ensure that biomarkers developed in one group of people are broadly applicable, something that needs high quality datasets from diverse populations to be made accessible to the research community.

“Our next steps as a consortium are to build tools to overcome some of these challenges and provide a platform for the systematic validation of aging biomarkers. We are also launching a biomarkers of aging competition to spur further innovation in this space.”