Not just a number: Science is redefining how we understand ageing

How do we measure ageing? In the words of management scholar Peter Drucker, “If you can’t measure it, you can’t improve it.” This principle applies equally well to today’s ageing research, where scientists are moving beyond simple numbers like chronological age to uncover deeper, biological insights.

Today, scientists recognize that biological age can differ substantially from chronological age, with individual variations mapped at the cellular and organ levels. In the rapidly expanding field of ageing biology research, the identification and evaluation of ageing biomarkers have become key goals. Recently developed “biologically informed” (based on biological pathways) and “causally guided” (anchored in disease prediction) epigenetic biomarkers offer a more nuanced picture that could shape future health interventions and improve individual health outcomes. This understanding of biological age is further refined with the development of organ-specific ageing clocks, allowing us to explore how ageing varies at the level of individual organs.

Researchers used plasma proteins from specific organs to model ageing in major organs like the heart, brain, lungs and kidneys. This approach enabled them to create “organ age gaps” that track how certain organs age relative to others, capturing unique age-related information for each organ that could reveal susceptibility to specific diseases.

Recent advances in organ-specific ageing clocks have revealed that the biological ages of individual organs are reliable predictors of related disease risks. For example, an older biological age in the brain correlates with a higher risk of Alzheimer’s disease, while aged lungs signal increased susceptibility to conditions like chronic obstructive pulmonary disease (COPD). Particularly, a “youthful” brain and immune system stand out for their association with disease-free longevity. Individuals with youthful biomarkers in these systems show a notably reduced risk of mortality, underscoring how maintaining brain and immune health can be key to extending health span and achieving a longer, healthier life.

Epigenetic ageing clocks have helped us predict biological age quite accurately, but they usually offer a single age estimate without explaining the underlying mechanisms of ageing. However, a new approach, called “Ageome,” challenges the idea that one number can capture the full picture of an individual’s biological age. Ageome introduces a way to measure the biological age of various cellular pathways and functions simultaneously, recognizing that different parts of the body and its functions might age at different rates.

Instead of providing a single estimate, Ageome produces a high-dimensional map of biological ageing, capturing how different biological functions or “modules” within the body are ageing differently. This allows scientists to assess ageing more comprehensively within an individual, across populations and even across species. Importantly, Ageome has already revealed some surprising findings. For example, certain interventions, like cellular reprogramming, may rejuvenate some pathways while accelerating ageing in others. Additionally, when applied to human populations, Ageome’s pathway-specific insights showed promise in predicting disease risk — particularly cancer — more effectively than conventional ageing clocks.

By revealing these diverse ageing patterns, Ageome not only offers a more detailed view of how ageing unfolds within the body but also opens up new possibilities for targeted interventions, helping researchers identify specific pathways that could be addressed to improve health and longevity.

The natural next step is examining how we can use the precision offered by today’s advanced ageing clocks to improve healthcare.

As we better understand the different ageing rates across organs, cells and pathways, researchers are focusing on interventions that target specific aspects of the ageing process. From lifestyle changes to experimental therapies, these efforts aim to decelerate biological ageing, reduce disease risk and potentially extend healthy years.

In academia, this search has prompted the formation of collaborative initiatives like the Biomarkers of Aging Consortium, where scientists work to develop consensus on ageing biomarkers and evaluate their impact on health outcomes. Initial findings from these interventions show promise, as lifestyle factors like diet and exercise have already been shown to decelerate ageing in specific organs, while some medications are being tested for their anti-ageing effects on cellular functions. The ambitious vision behind these efforts is to discover interventions that might one day slow, pause or even reverse certain aspects of biological ageing.

Ultimately, by leveraging these advanced ageing clocks, we gain a powerful toolkit for assessing which interventions are most effective for extending healthspan, giving us a glimpse into a future where personalized, targeted strategies could help individuals maintain vitality and resilience as they age.

The authors would like to acknowledge the contributions of Kejun Albert Ying, Jesse Poganik, and Jinyeop Song, whose presentations at the “Interdisciplinary Discussion on How Can AI Transform Aging Research” organized by the Harvard Graduate Student Club, Interdisciplinary Discussion on Disease and Health, in October 2024 in Boston, Massachusetts, enriched this discussion of ageing science.