‘Biomarkers of aging – the momentum is palpable’

The inaugural Biomarkers of Aging Symposium signposts an optimistic future for the field, say the organizers.

Last month saw The Buck Institute play host to the inaugural Biomarkers of Aging Symposium. Organised by the Biomarkers of Aging Consortium, the full-day, in-person event set itself the task of establishing a robust foundation for collaborative longevity R&D efforts in order to augment human healthspan and lifespan; as might be expected, there was a particular focus on biomarkers of aging.

The Symposium welcomed more than 250 attendees from around the world and featured 10 insightful short talks, 5 panels delivered and led by key leaders and over 20 scientists showcasing their work in poster sessions. The speaker and panelist guest lists were crammed with longevity A-listers, including Nir Barzilai, Vadim Gladyshev, Peter Fedichev, Joe Betts-LaCroix, Kristen Fortney, Steve Horvath, David Furman, Andrea Maier and Eric Verdin.

The Symposium organized itself around four key themes:

  • Conceptual frameworks and theories of aging and biomarkers of aging
  • Assessment and validation of biomarkers of aging
  • Application of biomarkers of aging for identification and evaluation of longevity interventions
  • Challenges and opportunities for establishing reliable biomarkers of aging

Longevity.Technology: Decades of research have laid the groundwork for interventions that can slow, or even halt aging. As practitioners work to bring these interventions into clinical practice, the longevity space needs to agree standardized, clinically-validated tools that can not only measure the aging process, but assess the effectiveness of interventions and therapies, both in terms of lifespan and healthspan expansion. The science is accelerating rapidly, with new biomarker discoveries and diagnostic refinements happening all the time. The Symposium acknowledges that these developments mean setting robust standards is of paramount importance.

We caught up with Dr Jesse Poganik from the Symposium’s Organizing Committee to find out how the Symposium had gone (spoiler alert: it was a resounding success) and how the Consortium plans to move forward.

There is a huge interest in biomarkers of aging, and Dr Poganik explains that there was agreement in the field that now is the time to come together to push these tools forward and ultimately enable them to help people and improve healthy longevity.

'Biomarkers of aging – the momentum is palpable'
Dr Jesse Poganik is part of the Symposium’s Organizing Committee

“The momentum in this field is palpable now,” he says. “I think this was exemplified by our event, which really exceeded our expectations. We totally sold out and even had a sizable waitlist.”

So, why is now the right time to progress a consensus on reliable biomarkers? The answer is that you cannot move forward without collaboration and agreement, as Poganik explains.

“Consensus is essential for many reasons: it is a key component of regulatory approval and on a more fundamental level, translating a biomarker for clinical applications requires coordination across groups with diverse expertise, and particularly between researchers and clinicians. Advancing biomarkers of aging to the clinic is something that no individual or single research group will be able to do alone, so bringing the broader community together to work towards this common goal is the underlying thread of all of the work of the consortium.”

Of course, biomarkers taken to clinic need to be reliable, but defining reliability is an art in itself. The Biomarkers of Aging Consortium is tackling that through roadmap workgroups, groups of leading experts across the field who it works with in iterative rounds to establish consensus on key topics such as establishing the reliability of a biomarker. This model has worked out well for the Consortium and resulted in its first paper published in Cell, with a second paper soon to appear in Nature Medicine.

'Biomarkers of aging – the momentum is palpable'
Poster sessions that showcased research were a highlight of the day

“Our workgroups deal directly with this question of what is a reliable biomarker, and the fact that it’s taken us (at least) two detailed papers with many expert contributors highlights the complexity of the challenge,” says Poganik. “Briefly, we have adapted and extended FDA’s guidelines for biomarker evaluation (FDA-BEST) to biomarkers of aging, which are quite different from biomarkers of specific diseases. There are numerous hurdles a biomarker needs to clear to be considered reliable and validated, and we are just at the beginning of the journey for biomarkers of aging.”

The Consortium is hopeful, however, that these roadmap papers will lay out a clear path that the experts in the field believe will help to bring these tools to the clinic.

It is not just defining reliable biomarkers that is tricky – there are other fundamental challenges in the longevity space, as Poganik explains.

“One of my deep personal interests is the definition of aging, which underlies so much of the lack of consensus in the aging biology field (at least in my opinion). Unsurprisingly, this question came up at the Symposium, and a talk focused on defining aging had one of the most lively Q&A sessions of the whole day.”

Poganik references the Cell paper in which the Consortium established working definitions of aging and other key terms that it hopes will gain wide acceptance across the field.

“We don’t intend these to be the final and unchangeable definitions, but we identified the necessity of defining common ground for our work by formulating these working definitions,” Poganik explains, add that the manuscript took many months of work by the drafting team, and the vast majority of time was spent on reconciling these definitions to ensure that they represented broad consensus across the expert contributors. 

There is a whole raft of theories of aging, and this can present specific problems in itself.

“It is clear that no single theory of aging sufficiently explains the aging process.” Poganik explains. “Rather than a unified theory, I personally prefer an approach where we attempt to understand fundamental features of aging as a biological process, and published an opinion on this topic with Vadim Gladyshev in September. I also believe that biomarkers of aging are key to understanding these features. So they are really far reaching tools – they have clear promise for clinical applications, but also help us a lot in basic aging science research.”

What does 2024 look like for the Consortium? Preparations for the 2024 Biomarkers of Aging Symposium are already underway, and Poganik explains that the roadmap work will continue as the expert panels have a lot of material left to cover, and that several additional collaborative manuscripts are planned.

The Consortium has also launched Biolearn, an open source tool for biomarkers of aging.

“Biolearn houses harmonized datasets to benchmark biomarkers of aging, and also implements ~20 biomarkers accessible with a single line of code, and more will be added as we go along,” Poganik explains. “So you can come to Biolearn with either a dataset for which you want to apply a suite of biomarkers, or a new biomarker that you want to validate across multiple datasets. We anticipate that this will become a key tool for the biomarkers of aging community.”

'Biomarkers of aging – the momentum is palpable'
Discussion and collaboration were the order of the day

Also underway is the first biomarkers of aging challenge.

“We hope the challenge will incentivize innovation in the biomarker development space by giving rewards for the best performing biomarkers that can predict chronological age, mortality, and multimorbidity,” says Poganik, explaining the challenge will take place in phases over 2024 and 2025.

Phase 1, which will happen in Q2 2024, will be the Chronological Age Prediction Challenge, which has $30k in awards, and Phase 2, which has $70k in awards, will take place in Q3 2024 and consist of the mortality-based Longevity Prediction Challenge.

After a 2024 Winners’ celebration in November, 2025 will see a multi-morbidity themed Healthspan Prediction Challenge. This carries an awards value of at least $100k.

Healthspan was a hot topic at the Symposium; not only does it not have a good consensus definition at the moment, but Poganik explains that the point was repeatedly made at the event that healthy lifespan is important.

“People do not want to live longer if it means that the added years will be spent in poor health.”

Photos courtesy of Jesse Poganik / Max Kamrani / Biomarkers of Aging Consortium