Hallmarks of Aging
The 12 molecular mechanisms that define biological ageing
Definition
The Hallmarks of Aging are the fundamental cellular and molecular processes that, together, define biological ageing. The original formulation by López-Otín, Blasco, Partridge, Serrano, and Kroemer in Cell (2013) described 9 hallmarks; the 2023 update expanded them to 12. Each hallmark must meet three criteria: it must manifest during normal ageing, its experimental aggravation must accelerate ageing, and its experimental mitigation must slow ageing or extend longevity.
Detailed explanation
The 12 Hallmarks (2023 update):
Primary hallmarks (causes of damage): 1. Genomic instability 2. Telomere shortening 3. Epigenetic alterations 4. Loss of proteostasis 5. Macroautophagy disabled (NEW 2023)
Antagonistic hallmarks (responses that can be either protective or pathological): 6. Deregulated nutrient sensing (mTOR, IGF-1, AMPK, sirtuins) 7. Mitochondrial dysfunction 8. Cellular senescence
Integrative hallmarks (functional consequences): 9. Stem cell exhaustion 10. Altered intercellular communication 11. Chronic inflammation (inflammaging) (NEW 2023) 12. Dysbiosis (NEW 2023)
This taxonomy is the unifying conceptual framework of modern longevity medicine. Each therapeutic intervention can be mapped to one or several hallmarks: metformin acts on nutrient sensing (#6); senolytics on senescence (#8); IV NAD+ on mitochondrial dysfunction (#7) and epigenetic alterations (#3); FMT on dysbiosis (#12). An ideal longevity protocol should target multiple hallmarks simultaneously, as they feed back into each other.
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