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Article History

Received: 26 June 2026

Accepted: 4 September 2026

First Online: 17 September 2026

Declarations

Patents: Certain therapeutic, diagnostic, and translational applications related to the TyrRS cascade are the subject of pending patent applications assigned to or licensed by Functional Longevity Labs, Inc.

Use of AI-assisted tools: During the preparation of this manuscript, the authors used an AI assistant (Perplexity) to assist with literature synthesis, drafting, and language editing. All scientific hypotheses, claims, and interpretations are the authors’ own.

Competing interests: W.S. is founder and chief executive of Functional Longevity Labs, Inc. (FLL) D.S., S.M., and D.I. are scientific advisors to FLL. W.S., S.M., and D.S. hold equity positions in FLL, a privately held company developing therapeutics in the class described in Sect. ‘‘ ’’. A lead preclinical candidate from this program has been disclosed publicly as a poster at the Alzheimer’s Association International Conference (Smith, Sajish, & Seiden, FLL-001, a first-in-class YARS1 modulator in preclinical development for Alzheimer’s disease; AAIC 2026, London, UK, July 12–15, 2026; Control No. 2026-DTA-13223-AAIC). Compound structure, pharmacokinetic parameters, and safety-pharmacology data are proprietary and are not relied upon in the present manuscript; no proprietary data appear in any figure or table. The cascade model and the chronomodulator design criteria advanced here are intended as a class-level, mechanistic framework testable with any agent meeting the Sect. ‘‘ ’’ specification and are presented independently of any specific clinical-stage asset.