Intermittent time-restricted eating may increase autophagic flux in humans: an exploratory analysis.

Date

2025

Authors

Bensalem, J.
Teong, X.T.
Hattersley, K.J.
Hein, L.K.
Fourrier, C.
Dang, L.V.P.
Singh, S.
Liu, K.
Wittert, G.A.
Hutchison, A.T.

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Journal of Physiology, 2025; 603(10):3019-3032

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Julien Bensalem, Xiao Tong Teong, Kathryn J.Hattersley, Leanne K. Hein, Célia Fourrier, Linh V. P. Dang, Sanjna Singh, Kai Liu, Gary A. Wittert, Amy T. Hutchison, Leonie K. Heilbronn, and Timothy J. Sargeant

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Abstract

Autophagy slows age-related pathologies and is stimulated by nutrient restriction in animal studies. However, this has never been shown in humans. We measured autophagy using a physiologically relevant measure of autophagic flux (flux ofMAP1LC3B isoformII/LC3B-II in peripheral blood mononuclear cells in the context of whole blood) in 121 humans with obesity who were randomised to standard care (SC, control condition), calorie restriction (CR) or intermittent fasting plus time-restricted eating (iTRE) for 6months.While the differences in change frombaseline between groups was not significant at 2 months, we observed a significant difference in change from baseline between iTRE compared to SC at 6 months (P = 0.04, post hoc analysis). This effect may be driven partly by a tendency for autophagy to decrease in the SC group. The difference in change from baseline between CR and SC was not significant. Uncorrected analysis of correlations showed a negative relationship between change in autophagy and change in blood triglycerides. Data on the specificity and performance of the methods used to measure human autophagy are also presented. This shows autophagy may be increased by intermittent nutrient restriction in humans. If so, this is a demonstration that nutrient restriction can be used to improve a primary hallmark of biological ageing and provides a mechanism for how fasting could delay the onset of age-related disease.

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© 2025 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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