Study

Long-term impact of caloric restriction on liver health and cell survival in a mouse model

Gökçe K, Doğan A, Akbari AM, Açık H, Midi A, Sheikhvatan M

PREPRINT; LONGITUDINAL MOUSE COMPARISON OF AD-LIBITUM, CHRONIC AND INTERMITTENT CALORIC RESTRICTION 2026

In 97 aging male mice, caloric restriction produced regimen- and age-dependent liver apoptosis and anti-apoptotic changes rather than one uniform effect.

DesignPREPRINT; LONGITUDINAL MOUSE COMPARISON OF AD-LIBITUM, CHRONIC AND INTERMITTENT CALORIC RESTRICTION
TierTier 3, Ingredient RCT (matching dose)
Year2026
JournalResearch Square preprint
N97
PublishedSep 21, 2026
Added to NO1GEVITYSep 27, 2026

Gökçe and colleagues followed 97 male C57BL/6 mice in ad-libitum, chronic caloric-restriction and intermittent-restriction groups. Chronic restriction reduced intake by 25%; the intermittent group alternated three weeks of unrestricted feeding with three weeks at 50% restriction. At 49 weeks, the restricted groups had higher hepatocyte caspase-3, a marker of apoptosis, than controls. At 85 weeks, chronic restriction was associated with higher BCL-2 in Kupffer cells, an anti-apoptotic signal. The abstract presents these as age- and regimen-dependent liver responses rather than a simple claim that restriction uniformly improves or harms the liver. The work matters because caloric restriction is often treated as a single intervention, while dose pattern and tissue context can change the biology. It remains a mouse preprint, uses only male animals, and reports molecular markers rather than human liver function, frailty or survival. The findings do not weaken the human caloric-restriction evidence base by themselves, but they argue for careful interpretation of tissue-specific mechanisms.

Caloric restriction may exert age- and regimen-dependent effects on liver cell survival pathways.
Critic notes

Preprint, male mouse model and molecular endpoints. No human outcome and no direct evidence that the reported marker changes alter healthspan.

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