Abstract

Caffeine, a methylxanthine derived from plants, is the most widely consumed ingredient in daily life. Therefore, it is necessary to investigate the effects of caffeine intake on essential biological activities. In this study, we attempted to determine the possible anti-aging effects of long-term caffeine intake in the intestine of an aged Caenorhabditis elegans model. We examined changes in intestinal integrity, production of vitellogenin (VIT), and mitochondrial function after caffeine intake. To evaluate intestinal aging, actin-5 (ACT-5) mislocalization, lumenal expansion, and intestinal colonization were examined after caffeine intake, and the levels of vitellogenesis as well as the mitochondrial activity were measured. We found that the long-term caffeine intake (10 mM) in the L4-stage worms at 25 °C for 3 days suppressed ACT-5 mislocalization. Furthermore, the level of autophagy, which is normally increased in aging animals, was significantly reduced in these animals, and their mitochondrial functions improved after caffeine intake. In addition, the caffeine-ingesting aging animals showed high resistance to oxidative stress and increased the expression of antioxidant proteins. Taken together, these findings reveal that caffeine may be a potential anti-aging agent that can suppress intestinal atrophy during the progression of intestinal aging.

Highlights

  • The physiological effects of caffeine intake have been reported to be beneficial or harmful, depending on the dose of intake [1,2,3,4]

  • Among the caffeine groups, long-term caffeine intake was the most effective in preventing intestinal atrophy during aging (Supplementary Figure S2). These results suggest that caffeine intake exerts a preventive effect on intestinal aging, and long-term caffeine intake is effective in aging C. elegans

  • We demonstrated that the intestinal aging phenotypes, including pharyngeal deterioration, intestinal atrophy, ACT-5 mislocalization, bacterial colonization, VIT production, and pseudocoelomic lipoprotein pool (PLP) accumulation were significantly suppressed by long-term caffeine intake

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Summary

Introduction

The physiological effects of caffeine intake have been reported to be beneficial or harmful, depending on the dose of intake [1,2,3,4]. C. elegans is an excellent animal model for studying the effects of caffeine intake on aging processes based on various indicators, including the degeneration of pharynx, presence of tumors in the uterus, atrophy of the intestine and gonads, and accumulation of lipoproteins in the body cavity [14]. We recently reported that caffeine intake reduces VIT production during the adult stage of C. elegans [4] Based on these findings, we hypothesized that caffeine intake could ameliorate intestinal atrophy, prevent intestinal aging, and eventually extend the lifespan of these aging animals by inhibiting the production of VIT

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