# Less is more: calorie restriction as a therapeutic for mental health disorders

**Authors:** Jason C. D. Nguyen, Antonina Govic, Elizabeth A. Levay, Matthew D. Zelko, Thiruma V. Arumugam, Jim Penman, Terrance G. Johns, Zoran Boskovic

PMC · DOI: 10.3389/fpsyt.2025.1584890 · 2025-06-16

## TL;DR

Calorie restriction and its mimetics may help treat anxiety, depression, and addiction by improving mental health and mimicking the effects of diet restriction.

## Contribution

The paper proposes novel molecular signatures for screening new calorie restriction mimetics.

## Key findings

- Calorie restriction improves anxiety-, depression-, and addiction-like symptoms and behaviors.
- CR mimetics show similar benefits without dietary restriction.
- Novel molecular signatures could aid in identifying new CRM candidates.

## Abstract

Anxiety, depression, and substance use disorders are prevalent mental health disorders that have debilitating health outcomes, and current treatment options are not always efficacious or tolerable. Calorie restriction (CR) has various health benefits, with research efforts focused on its effects in improving metabolic health and delaying biological aging. Recent studies have indicated that CR can also improve anxiety-, depression- and addiction-like symptoms and behavior. Similar benefits have also been observed in studies investigating a range of CR mimetics (CRMs) - molecules that mimic one or more of the physiological effects of CR without dietary restriction - indicating that both CR and CRMs could be used to assist in treating these symptoms. Here, we summarize the current evidence for the potential use of CR and select CRMs in the treatment of anxiety, depression, and addiction, as well as the possible molecular mechanisms underlying these beneficial effects. Finally, we propose novel molecular signatures that could be exploited to screen for novel CRM candidates.

## Linked entities

- **Diseases:** anxiety (MONDO:0005618), depression (MONDO:0002050)

## Full-text entities

- **Diseases:** Anxiety (MESH:D001007), addiction (MESH:D019966), depression (MESH:D003866), mental health disorders (OMIM:603663)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12207231/full.md

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Source: https://tomesphere.com/paper/PMC12207231