WWP1 knockout in mice: metabolic effects under calorie restriction, but no clear lifespan change
In male mice, removing WWP1 did not markedly change the survival response to long-term calorie restriction, though older calorie-restricted knockout mice were modestly heavier and showed selectively increased fatty-acid synthesis proteins in epididymal white fat. [1]
Automatic summary · not editorially reviewed
The key findings
Male wild-type and Wwp1 knockout mice were fed freely or long-term at 70% of free intake and followed through their natural lifespan. [1]
Wwp1 deficiency did not markedly modify the survival response associated with calorie restriction. [1]
In epididymal white fat, WWP1 deficiency selectively increased calorie-restriction-induced, Srebp-1c-dependent proteins of de novo fatty acid synthesis, while liver lipid metabolism was unaffected. [1]
The source at a glance
- Study type / format
- Animal study in mice (abstract)
- Population / context
- Male wild-type and systemic Wwp1 knockout mice under free feeding or long-term calorie restriction.
- Summary based on
- Study abstract
- Original publication
- June 30, 2026
Calorie restriction and WWP1 in mice
Calorie restriction extends lifespan in many species. WWP1 is needed for diet-restriction longevity in the worm Caenorhabditis elegans, but its role in mammalian calorie restriction was unclear. The researchers therefore studied systemic Wwp1 knockout mice, in which the gene is removed throughout the body. Male wild-type and knockout mice received either food freely (ad libitum) or long-term calorie restriction at 70% of free intake and were followed through their natural lifespan.
Supporting source [1]
Survival and body weight in restricted mice
Wwp1 deficiency did not markedly modify the survival response linked to calorie restriction. Despite comparable food intake, calorie-restricted knockout mice after middle age were modestly heavier than calorie-restricted wild-type mice. In epididymal white adipose tissue, WWP1 deficiency selectively increased calorie-restriction-induced, Srebp-1c-dependent expression of proteins involved in de novo fatty acid synthesis. Liver lipid metabolism was unaffected. The authors conclude that WWP1 acts as a partial suppressor of calorie-restriction-driven fatty acid metabolism and limits energy storage and lipid retention in white fat.
Supporting source [1]
Mouse findings versus worm longevity
The results suggest that, unlike in C. elegans, WWP1 is not required for calorie-restriction-induced longevity in mammals. This is an abstract of a mouse study; the full text was not reviewed. The survival finding is described as no marked modification, not as proof of no effect. The weight and tissue findings are associations in mice and do not establish causes or benefits for human lifespan.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Findings come from male mice and do not establish effects in humans. The survival result is described as no marked modification, not as proof of no effect.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Nozaki Y, Miura K, Yajima K, Hoshino S, Tamori S, Mizunoe Y, Kobayashi M, Higami Y. · europepmc.org · June 30, 2026