Age-Related Decline in Intestinal Villus Length: A Cross-Sectional Study on the Human Gut

Background/Objectives: There is widespread agreement that age is a significant predictor of impaired response to nutritional support. This is generally attributed to anabolic resistance, with impaired absorption considered irrelevant/non-existent. However, animal models demonstrate age-related structural changes in the intestinal mucosa that may reduce absorptive capacity. We aimed to evaluate potential histological changes in the duodenal mucosa associated with aging. Methods: We conducted a single-center observational cross-sectional study. Ambulatory younger (18–45 years) and older (≥70 years) adults referred for upper endoscopy were included and underwent duodenal biopsies. Those biopsies were analyzed and compared for histological/histomorphometric changes, including villus length. Clinical and laboratory data were also recorded. Results: One hundred patients were included (46 men/54 women), 50 aged 18–45 years and 50 aged ≥70 years. There were no duodenal endoscopic changes. The median villus length was 0.35 mm (IQR 0.32–0.41 mm) in older people, lower than in younger adults (0.57 mm; IQR 0.47–0.68 mm) (p < 0.001). In a multivariable regression model including age, sex, and Charlson comorbidity index, age remained inversely associated with villus length (p < 0.001). Older participants also exhibited lower hemoglobin, iron, folate, vitamin B12, albumin and vitamin D levels, despite normal inflammatory markers. Conclusions: Aging is associated with histological changes in the intestinal mucosa, including villus shortening. These findings support the concept of mucosal aging as a distinct biological process. Villus shortening may reflect reduced absorptive surface area and could contribute to age-related nutritional vulnerability, although its functional implications remain to be determined.