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SIRT1s ability to deacetylate and thereby activate key proteins involved in ferroptosis, such as GPX4 and FOXO3A, positions it as a nodal point in the regulation of this cell death process

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Conservative combination protocol (if attempting) Rationale for conservative approach: No safety data available Both peptides slow gastric emptying significantly Risk of severe GI complications Start low, go slow principle Tirzepatide component: Follow standard FDA-approved titration Weeks 1-4: 2.5mg weekly Weeks 5-8: 5mg weekly Weeks 9-12: 7.5mg weekly Weeks 13-16: 10mg weekly Week 17+: 12.5mg weekly (or stay at 10mg) Some reach 15mg weekly (maximum) Cagrilintide component (reduced from standard): Start AFTER tirzepatide stabilized at therapeutic dose (week 13+) Week 13-16: 0.6mg weekly (lower than standard) Week 17-20: 1.2mg weekly Week 21-24: 1.8mg weekly (may be maximum tolerable) Consider 2.4mg only if tolerating perfectly Conservative dosing comparison: Why sequential is safer: Tirzepatide establishes baseline first Can attribute new side effects to cagrilintide Easier to manage one variable at a time Option to stop cagrilintide if intolerable Less overwhelming than both simultaneously Expected benefits: 18-25% total weight loss (conservative estimate) Potentially superior to tirzepatide alone (15-22%) But incremental benefit may be modest (3-5% additional) Use SeekPeptides to plan sequential peptide additions safely

doi: 10.1161/JAHA.122.028892 3

It has not been shown to improve mood, behavior or the ability to perform daily activities