#41. Medicine never extended life. It stopped children from dying.
Average lifespan doubled in a century. The maximum moved by nothing. Two different numbers. Almost everybody confuses them, including doctors. 🧊
Cells accumulate damage in the womb. Copying errors, broken repair, mutations inherited from both parents. Birth is not the starting line. 🧬
What is aging?
Not time. Damage. Molecular damage. The 2013 hallmarks framework names nine.
All nine, from López-Otín et al., 2013, in their three groups. 🧬
Primary. The damage itself. 💥.
Genomic instability - DNA damage stacks up from radiation, chemicals and your own metabolism. Repair enzymes miss some. The misses are permanent. 🧨.
Telomere attrition - chromosome end caps shorten with every division. Run out and the cell stops dividing or dies. ✂️.
Epigenetic alterations - the switches controlling which genes fire drift out of pattern. The code stays intact, the reading of it goes wrong. 🎚️.
Loss of proteostasis - protein folding quality control fails. Misfolded proteins aggregate. This is the Alzheimer's and Parkinson's road. 🧩
Antagonistic. Responses that turn against you. ⚔️
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Deregulated nutrient sensing - the insulin/IGF-1 and mTOR pathways misread food signals. Dial them down in animals and lifespan extends. Dial too far and they die. 🍽️
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Mitochondrial dysfunction - power plants leak. Less energy out, more reactive oxygen species damaging everything nearby. ⚡
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Cellular senescence - damaged cells stop dividing instead of dying. Useful anti-cancer brake. Then they sit there pumping inflammatory signals into healthy neighbours. 🧟
Integrative. What you actually feel. 🩸
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Stem cell exhaustion - the repair crew stops showing up. Tissues cannot replace what they lose. 🛠️
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Altered intercellular communication - signalling between cells goes chronically inflammatory. The field calls it inflammaging. 🔥
Worth knowing: the same authors expanded this to twelve in 2023, adding disabled macroautophagy, chronic inflammation and dysbiosis. So the framework everyone quotes is already outdated by three. 📈