Small intestinal disorders in the elderly

Thomson, A. B. R.

doi:10.1016/j.bpg.2009.10.009

Cited by 53 publications

(29 citation statements)

References 90 publications

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“…These data are consistent with a similar study performed on rats (Smits and Lefebvre, 1996), but differ from a model of premature aging, the klotho mouse, where reduced fecal output was linked to a decrease in food intake (Asuzu et al, 2011). Increases in the rate of nutrient absorption with age could also contribute to our observations, although this seems unlikely based on earlier studies, which suggest that the rate of absorption of nutrients from the small intestine is reduced with increasing age (Drozdowski and Thomson, 2006;Thomson, 2009). …”

Section: Effects Of Age On Fecal Output and The Properties Of Fecal Psupporting

confidence: 91%

Impaired colonic motility and reduction in tachykinin signalling in the aged mouse

Patel

Fidalgo

et al. 2014

Experimental Gerontology

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Section: Effects Of Age On Fecal Output and The Properties Of Fecal Psupporting

confidence: 91%

Impaired colonic motility and reduction in tachykinin signalling in the aged mouse

Patel

Fidalgo

et al. 2014

Experimental Gerontology

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“…Given PARK2's role in mitophagy and mitochondrial quality control (16,34,39), it is tempting to speculate that changes in mitochondrial function contribute to the impaired intestinal lipid absorption. Precedent for such a relationship was described in humans where mitochondrial DNA mutations resulting in respiratory chain defects were associated with reduced proliferation and increased apoptosis of colonic crypt cells taken from elderly subjects, who frequently present with intestinal malabsorption (36,44). Mutation of the proofreading function of the mitochondrial DNA polymerase gamma in mice, which results in progressive mitochondrial DNA mutation and dysfunction, is also associated with reduced dietary fat absorption (13,28,45).…”

Section: Discussionmentioning

confidence: 99%

Reduced intestinal lipid absorption and body weight-independent improvements in insulin sensitivity in high-fat diet-fed Park2 knockout mice

Costa

Huckestein

Edmunds

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Shulman GI, Jurczak MJ. Reduced intestinal lipid absorption and body weight-independent improvements in insulin sensitivity in high-fat diet-fed Park2 knockout mice. Am J Physiol Endocrinol Metab 311: E105-E116, 2016. First published May 10, 2016; doi:10.1152/ajpendo.00042.2016.-Mitochondrial dysfunction is associated with many human diseases and results from mismatch of damage and repair over the life of the organelle. PARK2 is a ubiquitin E3 ligase that regulates mitophagy, a repair mechanism that selectively degrades damaged mitochondria. Deletion of PARK2 in multiple in vivo models results in susceptibility to stress-induced mitochondrial and cellular dysfunction. Surprisingly, Park2 knockout (KO) mice are protected from nutritional stress and do not develop obesity, hepatic steatosis or insulin resistance when fed a high-fat diet (HFD). However, these phenomena are casually related and the physiological basis for this phenotype is unknown. We therefore undertook a series of acute HFD studies to more completely understand the physiology of Park2 KO during nutritional stress. We find that intestinal lipid absorption is impaired in Park2 KO mice as evidenced by increased fecal lipids and reduced plasma triglycerides after intragastric fat challenge. Park2 KO mice developed hepatic steatosis in response to intravenous lipid infusion as well as during incubation of primary hepatocytes with fatty acids, suggesting that hepatic protection from nutritional stress was secondary to changes in energy balance due to altered intestinal triglyceride absorption. Park2 KO mice showed reduced adiposity after 1-wk HFD, as well as improved hepatic and peripheral insulin sensitivity. These studies suggest that changes in intestinal lipid absorption may play a primary role in protection from nutritional stress in Park2 KO mice by preventing HFD-induced weight gain and highlight the need for tissue-specific models to address the role of PARK2 during metabolic stress. lipid absorption; mitophagy; PARK2; insulin resistance; liver; small intestine; obesity PARK2 IS A UBIQUITIN E3 LIGASE that was first identified in patients with autosomal recessive juvenile Parkinsonism (ARJP) and has since emerged as one of the most frequently mutated genes in this disorder (25,31). PARK2 is comprised of an NH 2 -terminal ubiquitin-like domain, a novel PARK2-specific domain, and two RING-finger domains separated by an inbetween RING-finger (IBR) domain in the COOH terminus (25, 32). PARK2 mutations resulting in ARJP typically lead to loss of E3 ligase activity and commonly occur within the COOH-terminal RING-finger or IBR domains (9). PARK2 acts as a multifunctional E3 ligase in that it cooperates with several E2 conjugating enzymes, such as UBCH7, UBCH8, and UBCH13/UEV1, and catalyzes mono-and polyubiquitination with Lys 48 and Lys 63 linkages, indicating proteasome-dependent and -independent effects of PARK2-mediated ubiquitination (9,11,17,41,53). Multiple PARK2 substrates have been reported, but it still remains unclear how loss of PARK2 E3 li...

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“…CD in the elderly has been reviewed and also likely reflects increased recognition of undiagnosed CD in this age group [8][9][10] . The estimated prevalenc e of CD in individuals in the United Kingdom between 45 to 76 years of age is approximately 1.2%.…”

Section: Epidemiologymentioning

confidence: 99%

Recent advances in celiac disease

Freeman

Chopra²,

Clandinin³

et al. 2011

WJG

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Celiac disease now affects about one person in a hundred in Europe and North America. In this review, we consider a number of important and exciting recent developments, such as clinical associations, HLA-DQ2 and HLA-DQ8 predispositions, the concept of potential celiac disease, the use of new imaging/endoscopy techniques, and the development of refractory disease. This review will be of use to all internists, pediatricians and gastroenterologists.

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Small intestinal disorders in the elderly

Cited by 53 publications

References 90 publications

Impaired colonic motility and reduction in tachykinin signalling in the aged mouse

Impaired colonic motility and reduction in tachykinin signalling in the aged mouse

Reduced intestinal lipid absorption and body weight-independent improvements in insulin sensitivity in high-fat diet-fed Park2 knockout mice

Recent advances in celiac disease

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