2. Academic Validation
  3. Methionine-supplemented longevity diet increases growth hormone, GLP-1, and FGF21; reduces frailty; and promotes healthspan

Methionine-supplemented longevity diet increases growth hormone, GLP-1, and FGF21; reduces frailty; and promotes healthspan

  • Cell Metab. 2026 Jun 23:S1550-4131(26)00225-1. doi: 10.1016/j.cmet.2026.05.015.
Maura Fanti 1,  Sebastian Brandhorst 1,  Gerardo Navarrete 1,  Arnold Diaz 1,  Giacomo Giuliani 1,  Dolly Chowdhury 1,  Gabriel C Antunes 2,  Todd E Morgan 1,  Louis Dubeau 3,  Valentina Villani 4,  Laura Perin 5,  Vasanti S Malik 6,  Frank B Hu 7,  Valter D Longo 8
Affiliations

Affiliations

  • 1 Longevity Institute, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
  • 2 Laboratory of Molecular Biology of Exercise, University of Campinas, Limeira, São Paulo, Brazil.
  • 3 Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • 4 GOFARR Laboratory, Children's Hospital Los Angeles, Division of Urology, Saban Research Institute, Los Angeles, CA, USA.
  • 5 GOFARR Laboratory, Children's Hospital Los Angeles, Division of Urology, Saban Research Institute, Los Angeles, CA, USA; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • 6 Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • 7 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • 8 Longevity Institute, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA. Electronic address: [email protected].
PMID: 42335894 DOI: 10.1016/j.cmet.2026.05.015
Abstract

Southern European countries have some of the highest life expectancies in the world, yet they display relatively high frailty. We examined different diets to identify compositions that promote both healthspan and strength in mice. The western and ketogenic diets increased fat mass and frailty and increased either Cholesterol or Insulin resistance, whereas a low-protein longevity diet, modeling the traditional Mediterranean and Okinawan diets but supplemented with methionine (LDMM), reduced fat mass and frailty while improving cardiometabolic markers. LDMM reduced insulin-like growth factor (IGF)-1 while increasing growth hormone, GLP-1, and Fibroblast Growth Factor (FGF)21, which was required for fat loss and Insulin sensitivity. Bimonthly cycles of a 4-day fasting-mimicking diet instead improved metabolic markers. A cross-sectional analysis of epidemiological data from over 200,000 men and women indicates that those with the highest animal protein intake tended to have a healthier lifestyle but had approximately double the prevalence of type 2 diabetes compared with those in the lowest intake group. These findings indicate that mostly plant-based low-amino-acid diets have the most potent effects on healthspan but require moderate methionine intake to minimize frailty.

Keywords

FGF21; GH; GLP-1; IGF-1; dietary intervention; insulin sensitivity; longevity; methionine; obesity; weight loss.

Figures
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