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Calorie restriction & fasting
Research brief

Chronic vs intermittent calorie restriction and liver cell signaling in aging male mice

In aging male C57BL/6 mice, chronic and intermittent calorie restriction changed liver cell-death and survival signaling in hepatocytes and Kupffer cells, and the pattern differed by age and regimen. This is a mouse study, not evidence about human liver health. [1]

Automatic summary · not editorially reviewed

The key findings

  1. Ninety-seven aging male C57BL/6 mice were assigned to Baseline, Ad Libitum, Chronic Caloric Restriction (25% restriction) and Intermittent Caloric Restriction (alternating 3-week periods of ad libitum feeding and 50% restriction) groups. [1]

  2. At 49 weeks, hepatocyte caspase-3 expression was significantly higher in the chronic restriction group and in ICR-RF than in the ad libitum group, while no significant differences were seen at 85 weeks. [1]

  3. At 85 weeks, Kupffer-cell BCL-2 expression was significantly higher with chronic restriction than with ad libitum feeding and ICR-RF. [1]

The source at a glance

Study type / format
Preclinical mouse study (abstract)
Population / context
Aging male C57BL/6 mice (97 animals)
Summary based on
Study abstract
Publication status
Preprint · peer-review status not confirmed
Original publication
September 21, 2026

Liver signaling in 97 aging male mice

The study examined how chronic and intermittent calorie restriction affect apoptotic and anti-apoptotic signaling in the liver of aging male C57BL/6 mice. Ninety-seven mice were assigned to Baseline, Ad Libitum, Chronic Caloric Restriction (25% restriction) and Intermittent Caloric Restriction (alternating 3-week periods of ad libitum feeding and 50% restriction) groups. Liver tissue was collected at predefined time points, and BCL-2 and caspase-3 immunoreactivity in hepatocytes and Kupffer cells was scored semi-quantitatively.

Supporting source [1]

Age- and regimen-dependent liver cell findings

At 49 weeks, hepatocyte caspase-3 expression was significantly higher in the chronic restriction group and in one intermittent group (ICR-RF) than in the ad libitum group; no significant differences appeared at 85 weeks. At 85 weeks, Kupffer-cell BCL-2 expression was significantly higher with chronic restriction than with ad libitum feeding and ICR-RF. The authors conclude that calorie restriction modulates hepatic apoptotic and anti-apoptotic signaling in an age- and regimen-dependent way, with distinct responses in hepatocytes and Kupffer cells.

Supporting source [1]

Mouse-only scope of the liver findings

The comparison is cell-specific: hepatocytes and Kupffer cells were assessed separately, and chronic and intermittent restriction were compared across stages of aging. The authors present the findings as a basis for understanding how different calorie-restriction regimens may influence hepatic cellular adaptation during aging and call for further studies on relevance to age-related liver health. Because this is an abstract of a mouse study, it does not show effects on human liver health or lifespan.

Supporting source [1]

How to interpret this

Abstract only; the full text was not reviewed. This is a mouse study, so the liver findings do not establish effects on human liver health or lifespan.

Based on the study abstract; the full paper, tables and supplementary data were not reviewed.

Source & supporting passages

[1]
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. · europepmc.org · September 21, 2026

Read the quoted passagesIn the language of the original source
  1. Finding 1 ↑

    A total of 97 mice were assigned
  2. Finding 2 ↑

    hepatocyte caspase-3 expression was significantly higher in
  3. Finding 3 ↑

    Kupffer-cell BCL-2 expression was significantly higher in

AI-assisted summary with linked source passages. No independent editorial or clinical review.

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