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Protein restriction reprograms the multi-organ proteomic landscape of mouse aging

ABSTRACT: We conducted an extensive study involving the collection of 41 mouse organs at eight distinct time points spanning the mouse lifespan and implemented a dietary intervention with varying protein intake for different age and sex groups. We also obtained plasma samples from both mice and humans to investigate the systemic effects of aging and PR.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Heart, Brain, Blood Plasma, Liver, Lung, Lymph Node, Colon, Kidney

SUBMITTER: Tian Lu

LAB HEAD: Tiannan Guo

PROVIDER: PXD053154 | Pride | 2025-10-26

REPOSITORIES: Pride

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			Action	DRS
	A20220206lut_Ag2_fpDIA_30min_b17_11_part1.raw	Raw
	A20220206lut_Ag2_fpDIA_30min_b17_11_part2.raw	Raw
	A20220206lut_Ag2_fpDIA_30min_b17_13_part1.raw	Raw
	A20220206lut_Ag2_fpDIA_30min_b17_13_part2.raw	Raw
	A20220206lut_Ag2_fpDIA_30min_b17_14_part1.raw	Raw

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Project description:Aims/hypothesis: Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of the metabolic syndrome. Nonetheless, it remains elusive whether the benefits of DR in humans are mediated by calorie or nutrient restriction. This study was conducted to identify whether isocaloric dietary protein restriction is sufficient to confer the beneficial effects of dietary restriction in patients with metabolic syndrome. Methods: We performed a prospective, randomized controlled dietary intervention under constant nutritional and medical supervision. A total of 21 individuals diagnosed with the metabolic syndrome was randomly assigned for caloric restriction (CR; n = 11, mean age 49 ± 8.5 years, female 63%; diet of 5,941 ± 686 KJ per day) or isocaloric dietary protein restriction (PR; n = 10, mean age 51.6 ± 8.9 years, female 50%; diet of 8,409 ± 2,360 KJ per day) and followed for 27 days. Results: Like CR, PR promoted weight loss (-6.6%, P= 0.0041) due to reduction in adiposity (-9.9%, P= 0.0007), associated with reductions in blood glucose (-52.7%, P= 0.0002), lipid levels (cholesterol, -35.4%, P= 0.0010; triglycerides, -39.5% P= 0.0022) and blood pressure (systolic, -37.7 P< 0.0001; diastolic, -73.2% P< 0.0001). PR resulted in enrichment of metabolic pathways related to the immune system such as B cell proliferation, lymphocyte proliferation and leukocyte proliferation in subcutaneous adipose tissue. Hence, a reduction in calorie intake or changes in the gut microbiome are not necessary to confer the metabolic benefits of DR. Instead, a reduction in protein intake with a mild increase in carbohydrate intake to maintain the isocaloric balance of the diet is sufficient to improve metabolic control. Conclusions/interpretation: Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has greater potential to be used as adjuvant therapy for people with the metabolic syndrome.

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Protein restriction reprograms the multi-organ proteomic landscape of mouse aging

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