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Proposed mechanisms of IGF1 mediated prevention of aging-associated ICC-SC decline. During aging, increased Trp53 reduces IGF1 in part by accumulating DNA damage. Reduced IGF1 inhibits ERK1/2 phosphorylation (P), leading to ICC-SC growth arrest by increasing CDKN1B and decreasing CCND1. IGF1 supplementation mitigates the ICC-SC decline by restoring reduced ERK phosphorylation and preventing DNA damage accumulation.
