Treating Aging Itself: The Case for Geroscience
Aging is the single largest risk factor for the diseases that kill most people, yet medicine treats those diseases one at a time rather than their shared upstream cause. This founding report surveys the biology of aging, the emerging geroscience hypothesis, the scientific and regulatory barriers to translation, and why directly targeting aging could be among the highest-leverage — if hardest — bets in global health.
Treating Aging Itself: The Case for Geroscience
Executive Summary
Every year, aging-related decline drives the overwhelming majority of deaths and a vast burden of chronic disease and disability. The geroscience hypothesis holds that the biological processes of aging are a common root cause of conditions as varied as cardiovascular disease, cancer, neurodegeneration, and type 2 diabetes — and that intervening in aging itself could compress or delay all of them simultaneously. The importance is near-maximal; the tractability is the genuine bottleneck.
The Scale of the Problem
A peer-reviewed decomposition of the Global Burden of Disease found that population ageing was associated with 12 million additional deaths in 2017 — 27.9% of all deaths worldwide that year. As populations age, the share of disease burden attributable to aging-related processes continues to climb. The economic value of even modest delays in aging has been estimated in the tens of trillions of dollars.
Why This Is Hard (Low Tractability)
- No validated human interventions: Promising candidates (senolytics, metformin, rapamycin analogues, partial reprogramming) remain unproven in rigorous human trials for healthspan extension.
- Unvalidated biomarkers: Without accepted measures of biological age, trials are slow and expensive — you cannot easily measure whether an intervention is working short of waiting decades.
- Regulatory non-recognition: Aging is not recognized as a treatable indication by major regulators, so there is no clear approval pathway. The TAME trial (metformin) was designed in part to establish one.
- Hype and noise: The field is crowded with unsupported claims, complicating credible prioritization.
The Neglectedness Landscape
Basic biology-of-aging research receives only a few hundred million dollars per year, dwarfed by disease-specific funding (the US National Institute on Aging's ~$4.5B budget skews heavily toward Alzheimer's). However, a surge of private longevity venture capital — on the order of $8.5 billion per year — moderates the overall neglectedness, even if it is concentrated in a handful of well-publicized companies.
Tractable Sub-Problems
- Biomarker validation: Developing and validating robust measures of biological age would unlock faster, cheaper trials.
- Regulatory pathway development: Establishing aging (or a proxy like multimorbidity) as an approvable indication.
- Rigorous trials of repurposed drugs with existing safety data (metformin, rapamycin).
- Foundational basic science on the hallmarks of aging.
Recommendations
- Fund biomarker-of-aging validation as a field-enabling public good.
- Support regulatory-science work to create an approval pathway.
- Back rigorous, well-powered human trials over speculative consumer interventions.
- Maintain epistemic discipline — distinguish credible geroscience from longevity hype.
Further Reading
- López-Otín et al., "The Hallmarks of Aging," Cell (2013, updated 2023)
- Chang et al., "Measuring population ageing," PLOS Medicine (2020)
- Barzilai et al., "Metformin as a Tool to Target Aging" (TAME), Cell Metabolism (2016)
- Scientific reports from the National Institute on Aging