Effects of Lifelong Intake of Lemon Polyphenols on Aging and Intestinal Microbiome

23 July 2026
Ali Alawadhi
Effects of Lifelong Intake of Lemon Polyphenols on Aging and Intestinal Microbiome

Abstract

  • Background

While dietary polyphenols have been widely investigated for their health-promoting properties primarily in short-term rodent models, their long-term physiological impacts following lifelong consumption remain largely unclear. Lemons (Citrus limon), which are globally consumed and rich in bioactive lemon polyphenols (LPP), possess recognized antioxidant and anti-inflammatory capacities, yet the specific effects of lifelong LPP intake on aging trajectories, lifespan parameters, and gut microbial homeostasis are unknown. This study was designed to systematically examine the anti-aging efficacy of lifelong LPP supplementation on physical phenotypes, aging-related clinical scores, locomotor activity, cognitive function, and the intestinal microbiome utilizing the senescence-accelerated mouse prone 1 (SAMP1) model alongside senescence-resistant control mice (SAMR1).

  • Methods

A long-term, controlled experimental design was conducted utilizing senescence-accelerated mouse prone 1 (SAMP1) and senescence-resistant mouse 1 (SAMR1) subjects. Mice were divided into experimental cohorts with continuous ad libitum access to drinking water (the SAMR1 control group, the P1 water-treated control group) or a 0.1% lemon polyphenol-supplemented water solution (the P1_LPP intervention group) throughout their entire lifespan. Throughout the multi-month intervention, systemic aging-related scores (such as the development of periophthalmic lesions), locomotor activity levels, and behavioral/cognitive functions were systematically tracked. Upon study termination, comprehensive microbiome analyses via 16S rRNA sequencing were performed on fecal samples to evaluate shifts in intestinal microbial structure, taxonomic distributions, and specific phylum-level ratios (including Bacteroidetes/Firmicutes and Lactobacillus abundances).

  • Results

Lifelong dietary intake of lemon polyphenols produced profound physiological and microbiological benefits in accelerated senescence subjects. Specifically, the P1_LPP group exhibited a statistically significant prolongation of lifespan by approximately 3 weeks compared to untreated controls, alongside a notable delay in the onset of aging-related clinical scores (such as periophthalmic skin lesions) and the prevention of age-related locomotor atrophy. Microbiome profiling revealed that while the untreated P1 water group underwent drastic age-associated structural shifts in the intestinal microbiome, the LPP-supplemented P1_LPP group maintained a stable microbial profile closely mirroring the healthy SAMR1 resistance phenotype. Furthermore, the altered Bacteroidetes/Firmicutes phylum ratio typically observed in aging controls was significantly normalized by LPP intake, and the age-associated excessive proliferation of Lactobacillus was significantly attenuated in the P1_LPP cohort.

  • Conclusions

Lifelong dietary intake of lemon polyphenols exerts significant anti-aging protective effects on both systemic physical phenotypes and the intestinal microenvironment. By prolonging lifespan, delaying physical senescence, and preserving gut microbial homeostasis, lifelong LPP supplementation emerges as an effective nutritional strategy to mitigate age-related physiological decline.



https://www.nature.com/articles/s41598-019-40253-x