An international consortium of geroscientists presents geromedicine, a translational framework that targets fundamental aging mechanisms—cellular senescence, mitochondrial dysfunction, dysregulated nutrient sensing, and stem cell exhaustion—using interventions like senolytics, rapalogs, and NAD+ precursors to compress morbidity and extend healthspan.
Key points
Defines geromedicine as targeting core aging processes rather than individual diseases
Highlights cellular senescence, mitochondrial dysfunction, nutrient sensing, and stem cell exhaustion as intervention points
Recommends senolytics, rapalogs, and NAD+ precursors in early‐phase human trials
Calls for composite endpoints, resilience biomarkers, and gerodiagnostics in clinical trials
Advocates regulatory reform to accommodate pleiotropic effects of aging‐targeted therapies
Why it matters:
By reframing aging as a treatable condition, geromedicine shifts the focus from disease‐by‐disease management to proactive healthspan extension. This paradigm could reduce the burden of multiple chronic diseases, optimize resource allocation in healthcare, and prompt regulatory frameworks to evaluate interventions holistically, paving the way for more effective aging‐targeted therapies.
Q&A
What is geromedicine?
What are cellular senescence and its role in aging?
How do composite endpoints improve gerotherapeutic trials?
What are gerodiagnostics?
Why is regulatory evolution necessary for geromedicine?
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Academy
Introduction to Geromedicine
Geromedicine is an emerging field that treats aging itself as a clinical target. Unlike traditional medicine, which addresses individual diseases after they arise, geromedicine seeks to intervene in the biological processes that underlie multiple age-related conditions. By doing so, it aims to delay the onset of illnesses such as cardiovascular disease, diabetes, neurodegeneration, and frailty, thereby extending the period of healthy life, or healthspan. This approach integrates genetic, molecular, and clinical research to propose therapies that can be tested in humans.
Hallmarks of Aging as Targets
Research in geroscience has identified several hallmarks of aging—key biological mechanisms that drive the decline in tissue and organ function over time. These include:
- Cellular Senescence: Cells that permanently stop dividing and secrete inflammatory factors contribute to tissue damage and chronic inflammation.
- Mitochondrial Dysfunction: Decline in mitochondrial performance leads to reduced energy production and increased oxidative stress.
- Dysregulated Nutrient Sensing: Pathways such as mTOR, AMPK, and insulin/IGF-1 signaling become imbalanced, affecting metabolism and growth.
- Stem Cell Exhaustion: Loss of regenerative capacity in tissues impairs repair and maintenance mechanisms.
Key Interventions
Geromedicine explores various therapeutic strategies that modulate these hallmarks:
- Senolytics: Small molecules that selectively clear senescent cells to reduce inflammation and improve tissue function.
- Rapalogs (e.g., Rapamycin): Drugs that inhibit mTOR signaling, promoting cellular maintenance and stress resistance.
- NAD+ Precursors: Supplements like NMN and NR aim to boost cellular NAD+ levels, enhancing mitochondrial performance and DNA repair.
Diagnostics and Biomarkers
To measure intervention effects, geromedicine uses gerodiagnostics, which quantify biological age and resilience. Tools include:
- Epigenetic Clocks: DNA methylation patterns as predictors of biological versus chronological age.
- Proteomic and Multi-omic Signatures: Panels of proteins, metabolites, and transcripts reflecting molecular health.
- Functional Biomarkers: Physical performance tests and clinical measures indicating overall healthspan improvements.
Regulatory and Clinical Trial Innovations
Traditional regulatory frameworks focus on single-disease outcomes, which are misaligned with gerotherapeutics’ multi-system benefits. Geromedicine advocates for:
- Composite Endpoints: Combining disease incidence, functional measures, and biomarker changes into a unified trial outcome.
- Time to Multimorbidity Metrics: Evaluating delays in the onset of multiple age-related conditions.
- Resilience Testing: Assessing how well individuals recover from stressors or illness as a metric of aging.rate
By adopting these innovations, clinical trials can better capture the true impact of aging-targeted therapies and facilitate their approval, ultimately transforming healthcare for aging populations.