Ergothioneine and age-related circadian decline in mouse cells
In mouse embryonic fibroblasts, chronic ergothioneine treatment increased the amplitude of the PER2::LUC rhythm dose-dependently, and co-treatment partly restored rhythm changes caused by the NAMPT inhibitor FK866, which was used to model NAD decline. [1]
Automatic summary · not editorially reviewed
The key findings
In PER2::LUC mouse embryonic fibroblasts, chronic ergothioneine treatment enhanced rhythm amplitude dose-dependently without markedly altering baseline period length. [1]
FK866, a NAMPT inhibitor used to model NAD decline, reduced rhythm amplitude, lengthened the period and increased cycle-to-cycle variability; ergothioneine co-treatment restored amplitude, attenuated period lengthening and reduced variability. [1]
Ergothioneine increased the NAD/NADH ratio under basal conditions and elevated NAD levels and the NAD/NADH ratio under FK866-induced NAD depletion; the authors state this was not solely cytoprotection. [1]
The source at a glance
- Study type / format
- Preclinical cell-culture study (abstract)
- Population / context
- PER2::LUC mouse embryonic fibroblasts in cell culture
- Summary based on
- Study abstract
- Original publication
- July 11, 2026
Mouse fibroblast clock and NAD-depletion model
The abstract describes experiments in PER2::LUC mouse embryonic fibroblasts. Aging-related circadian decline was not studied in aged animals; instead, NAD decline was modeled with FK866, a NAMPT inhibitor that depletes intracellular NAD. FK866 reduced rhythm amplitude, lengthened the period and increased cycle-to-cycle variability. The authors state that declining NAD levels and SIRT1 activity have been implicated in age-associated circadian disruption.
Supporting source [1]
Ergothioneine effects on rhythm and NAD measures
Chronic ergothioneine treatment enhanced the amplitude of the PER2::LUC rhythm in a dose-dependent manner without markedly altering baseline period length. With FK866, co-treatment with ergothioneine significantly restored rhythm amplitude, attenuated FK866-induced period lengthening and reduced period variability. Biochemically, ergothioneine increased the NAD/NADH ratio under basal conditions and significantly elevated both NAD levels and the NAD/NADH ratio under FK866-induced NAD depletion. The authors state this effect was not attributable solely to cytoprotection.
Supporting source [1]
Cell-model scope and proposed nutritional idea
The study concludes that ergothioneine enhances circadian rhythm robustness and counteracts NAD-depletion-induced clock dysfunction in this cell model. The authors suggest ergothioneine may ameliorate age-related circadian decline by improving intracellular redox balance and NAD metabolism. Because ergothioneine crosses the blood-brain barrier, they propose it as a possible novel nutritional strategy to preserve circadian function during aging. These are proposals from a cell-based abstract, not demonstrated human lifespan or health benefits.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Findings come from mouse embryonic fibroblasts, with FK866 used to model NAD decline rather than aged animals or humans. No human outcomes, lifespan or clinical benefit are reported. The nutritional-strategy idea is a proposal, not a tested intervention.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Wakita K, Watanabe K, Nakamura TJ. · europepmc.org · July 11, 2026