Oct 7 (edited) • 📚 Content & Research
Hallmarks of Aging
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🔑 The Core 9 Hallmarks (López-Otín, 2013)
- Genomic instability – DNA damage from ROS, replication errors, toxins.
- Telomere attrition – Chromosome shortening leading to senescence.
- Epigenetic alterations – Disrupted DNA methylation, histone modification, chromatin remodeling.
- Loss of proteostasis – Protein misfolding/aggregation (e.g., Alzheimer’s).
- Deregulated nutrient sensing – Overactive mTOR/insulin vs. protective AMPK, sirtuins.
- Mitochondrial dysfunction – Declining ATP, mtDNA mutations, oxidative stress.
- Cellular senescence – Accumulation of pro-inflammatory “zombie cells.”
- Stem cell exhaustion – Reduced regenerative capacity.
- Altered intercellular communication – Inflammaging and impaired immunosurveillance.
🚀 Expanded Hallmarks (2021–2023)
- Dysbiosis – Gut microbiome imbalance driving systemic inflammation.
- Chronic inflammation – Persistent cytokine activity (IL-6, CRP).
- Disabled autophagy – Failure to clear damaged proteins/organelles.
- ECM stiffening – AGE cross-links reduce tissue elasticity.
- Altered mechanical properties – Mechanobiological decline in tissue resilience.
- Cellular enlargement – Senescent hypertrophic cells with impaired function.
- Splicing dysregulation – RNA processing errors linked to cancer and metabolic disease.
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Hallmarks of Aging
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