Decreased lipid absorption due to reduced pancreatic lipase activity in aging male mice

Abstract

Malnutrition due to aging is partly caused by decreased absorption of nutrients by the gastrointestinal tract. However, the underlying mechanism is unclear and changes in lipid absorption with aging are poorly understood. In this study, changes in lipid absorption with aging were examined in mice aged 3 and 25 months. After overnight fasting, blood samples were collected from snipped tails and then soybean oil was administered orally. Three hours later, mice were sacrificed by decapitation and the liver, pancreas, small intestine and blood were collected. The increase in serum triacylglycerol after soybean oil administration was significantly lower in the older mice, indicating a decrease in lipid absorption with aging. Measurement of mRNA levels for triacylglycerol absorption-related genes showed that mRNA for pancreatic lipase tended to decrease in 25-month-old mice. There was no significant difference in the protein level of pancreatic lipase, but the enzyme activity showed a significant decrease in the older mice. To examine this mechanism, expression levels of mRNA for protein turnover-related genes in the pancreas were measured. The level of a proteasomal mRNA showed a significant decrease in 25-month-old mice. This suggests that the ability to degrade unfolded protein decreases in the aging pancreas, and that this leads to reduction of pancreatic lipase activity and a decrease in lipid absorption.

Low-Density Lipoprotein Cholesterol and Alzheimer's Disease: A Systematic Review and Meta-Analysis

“…In current meta-analysis, subgroup analysis on age showed LDL-c levels higher in AD patients aged 60-70 than that of non-dementia, but no association of AD with LDL-c in patients over the age of 70, indicating that the neurotoxic role of LDL-c in AD may only apply to individuals aged 60-70 and gradually subsides with advancing age. These results were consistent with the Washington Heights/Inwood Columbia Aging Project (Helzner et al, 2009), presumably that enzymatic activity and mRNA level of pancreatic lipase decreased with advancing age (Yamamoto et al, 2014), so did lipid ingestion and absorption, and thus to abnormal LDL-c metabolism. Cardiovascular disease contributes to AD, and both of them mutually affect respective pathological processes (Liu et al, 2014;Bleckwenn et al, 2017), which is consistent with our findings of meta-regression.…”

Influence of Age and Body Mass Index on Total and Segmental Colonic Transit Times in Constipated Subjects

“…It was previously shown that age was associated with constipation via the modification of motor and secretory functions of the gastrointestinal tract. 26 The first result was the importance of age in the left CTT and RSTT in constipated subjects. There were no differences of mean age, and total and segmented CTTs amongst the different clinical groups of constipated patients.…”

The ageing gastrointestinal tract

“…For example, in older (25 months old) compared with younger (3 months old) mice, serum triacylglycerol concentrations increased 5% less after soybean oil ingestion [40]. The mechanisms underlying these changes in lipid absorption with ageing were also examined by Yamamoto et al [40] based on the measurement of expression levels of mRNA for triacylglycerol absorption-related genes. The mRNA level for pancreatic lipase, which is required for triacylglycerol hydrolysis, was 55% lower in the pancreas of the older than younger mice.…”