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In 2023, Lopez-Otin proposed twelve markers of aging, including genomic instability, telomere loss, epigenetic changes, loss of protein balance, failure of macroautophagy, dysregulated nutrient sensing, mitochondrial dysfunction, cell senescence, stem cell depletion, altered intercellular communication, chronic inflammation, and dysbiosis

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However, in this latter case, other counter-regulatory mechanisms (internalization, traffic of OR) could participate to desensitization making its description complex