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Open problems in ageing science: A roadmap for biogerontology

Published 24 Jul 2025 in q-bio.OT | (2507.18602v1)

Abstract: The field of ageing science has gone through remarkable progress in recent decades, yet many fundamental questions remain unanswered or unexplored. Here we present a curated list of 100 open problems in ageing and longevity science. These questions were collected through community engagement and further analysed using Natural Language Processing to assess their prevalence in the literature and to identify both well-established and emerging research gaps. The final list is categorized into different topics, including molecular and cellular mechanisms of ageing, comparative biology and the use of model organisms, biomarkers, and the development of therapeutic interventions. Both long-standing questions and more recent and specific questions are featured. Our comprehensive compilation is available to the biogerontology community on our website (www.longevityknowledge.app). Overall, this work highlights current key research questions in ageing biology and offers a roadmap for fostering future progress in biogerontology.

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Open Problems

  1. Why do we age? 
  2. Do fundamental ageing processes exist and if so, how do they synchronize ageing changes and promote age-related diseases? 
  3. Which tissues, organs or cell types contribute more to ageing? 
  4. Does somatic mutation accumulation cause ageing? 
  5. What molecular and cellular processes modulate the pace of ageing in mammals? 
  6. Which and when are senescent cells beneficial and detrimental? 
  7. What mechanisms determine the longevity of long-lived species? 
  8. Which ageing changes in model organisms also change in a similar way in humans? 
  9. How can we measure intrinsic biological age in individuals and translate this knowledge into accurate biomarkers of ageing? 
  10. How can we reverse or restore cell function lost during ageing? 
  11. How can we measure the extent and pace of changes in the homeodynamic space during ageing? 
  12. How can we break through the current human lifespan ceiling of 122 years? 
  13. How and which interventions should be prioritized for human clinical trials? 
  14. Can a combination of senolytics with ROCK inhibitors and 5-LOX inhibitors contribute to tissue rejuvenation? 
  15. Can we apply stem cell therapy based on our own young stem cells (e.g., from cord blood) to modulate ageing? 
  16. Could blood clean-up be used to target ageing processes? 
  17. How much does the immune response to mutated cells or altered (oxidized, misfolded) molecules (e.g. oxLDL, beta amyloid, alpha synuclein) contribute to ageing? 
  18. How much do positive feedback loops and chain reactions contribute to ageing? 
  19. How many diseases of ageing are caused by the trapping of citrate in the mitochondria? 
  20. Drivers of ageing remain open to debate 

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