Loss of Cell Identity Drives Human Aging
6 hours ago
- Two recent papers propose a new model of aging focusing on loss of cell identity, complementing the traditional wear-and-tear model.
- Cellular identity is established epigenetically and maintained by a three-tier regulatory grammar; the slow layer, involving chromatin architecture, locks in cell identity.
- Aging causes epigenetic erosion (decanalization) of Waddington's landscape, leading to loss of cell identity and mesenchymal drift, which results in fibrosis and inflammation.
- Mesenchymal drift is linked to numerous age-related diseases, including atherosclerosis, macular degeneration, and Alzheimer's.
- Potential interventions to preserve or restore cell identity include caloric restriction, partial epigenetic reprogramming (Yamanaka factors), and lithium.
- The epigenetic clock measures the erosion of PRC2-mediated slow layer architecture, and lifestyle factors like diet and sleep can impact aging.