Age‐related changes in bile acid synthesis and hepatic nuclear receptor expression

Bertolotti, Marco; Gabbi, Chiara; Anzivino, Claudia; Crestani, Maurizio; Mitro, Nico; Puppo, Marina Del; Godio, Cristina; Fabiani, Emma De; Macchioni, Daria; Carulli, Lucia; Rossi, Aldo; Ricchi, M.; Loria, Paola; Carulli, Nicola

doi:10.1111/j.1365-2362.2007.01808.x

Cited by 59 publications

(49 citation statements)

References 47 publications

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“…A decline in bile acid synthesis and hepatic expression of CYP7A1 have been shown to be correlated with ageing in human subjects (Bertolotti et al, 2007). This decreases cholesterol utilisation for the de novo synthesis of bile acids (Bertolotti et al, 2007). This is supported by Bertolotti et al (1993) who carried out a linear regression analysis which estimated that the amount of cholesterol undergoing the CYP7A1 regulated reaction in humans decreases by 60mg per day, every 10 years (Bertolotti et al, 1993).…”

Section: How Cholesterol Metabolism Changes With Agementioning

confidence: 96%

“…Additionally, this could be due to the decreased demand for cholesterol for the de novo synthesis of bile acid, due to the age-related decrease in bile acid synthesis (Ericsson et al, 1991). A decline in bile acid synthesis and hepatic expression of CYP7A1 have been shown to be correlated with ageing in human subjects (Bertolotti et al, 2007). This decreases cholesterol utilisation for the de novo synthesis of bile acids (Bertolotti et al, 2007).…”

Section: How Cholesterol Metabolism Changes With Agementioning

confidence: 99%

“…Specifically, there is 1) an age-related decline in hepatic LDLr and subsequent reduction in LDL-C clearance (Millar et al, 1995), 2) an increase in cholesterol absorption (Duan et al, 2006), 3) a decline of BSH-positive intestinal microflora, such Lactobacillus and Bifidobacterium species (Hopkins and Macfarlane, 2002), and 4) a decline in bile acid synthesis (Bertolotti et al, 2007). To represent the ageing process, 4 parameters were modified.…”

Section: Ageingmentioning

confidence: 99%

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Mathematically modelling the dynamics of cholesterol metabolism and ageing

et al. 2016

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Section: How Cholesterol Metabolism Changes With Agementioning

confidence: 96%

Section: How Cholesterol Metabolism Changes With Agementioning

confidence: 99%

Section: Ageingmentioning

confidence: 99%

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Mathematically modelling the dynamics of cholesterol metabolism and ageing

et al. 2016

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“…Bertolotti et al (63) estimated by linear regression analysis a 60 mg/d (about 150 µM/ d) decline every 10 years, in cholesterol undergoing cholesterol 7α-hydroxylation, while Einarsson et al (64) estimated an 80 mg/d (200 µM/d) reduction over the same time period. Bertolotti et al (62) propose the age-related reduction in CYP7A1 expression could be related to the concomitant decline in hepatic nuclear factor four and co-activator CYP7A1 promoter-binding factor/liver receptor homologue-1, mediated by the decline in growth hormone and insulin-like growth factor.…”

Section: Intrinsic Ageingmentioning

confidence: 99%

Investigating cholesterol metabolism and ageing using a systems biology approach

et al. 2016

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CVD accounted for 27 % of all deaths in the UK in 2014, and was responsible for 1·7 million hospital admissions in 2013/2014. This condition becomes increasingly prevalent with age, affecting 34·1 and 29·8 % of males and females over 75 years of age respectively in 2011. The dysregulation of cholesterol metabolism with age, often observed as a rise in LDL-cholesterol, has been associated with the pathogenesis of CVD. To compound this problem, it is estimated by 2050, 22 % of the world's population will be over 60 years of age, in culmination with a growing resistance and intolerance to pre-existing cholesterol regulating drugs such as statins. Therefore, it is apparent research into additional therapies for hypercholesterolaemia and CVD prevention is a growing necessity. However, it is also imperative to recognise this complex biological system cannot be studied using a reductionist approach; rather its biological uniqueness necessitates a more integrated methodology, such as that offered by systems biology. In this review, we firstly discuss cholesterol metabolism and how it is affected by diet and the ageing process. Next, we describe therapeutic strategies for hypercholesterolaemia, and finally how the systems biology paradigm can be utilised to investigate how ageing interacts with complex systems such as cholesterol metabolism. We conclude by emphasising the need for nutritionists to work in parallel with the systems biology community, to develop novel approaches to studying cholesterol metabolism and its interaction with ageing.

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“…Consequently, the data are inconsistent [13,14]. Bertolotti et al [15] recently found a negative correlation between age and serum C4 concentrations and also with age and hepatic cholesterol 7a-hydroxylase m-RNA expression.…”

Section: Introductionmentioning

confidence: 99%

The Bile Acid Turnover Rate Assessed with the 75SeHCAT Test Is Stable in Chronic Diarrhoea but Slightly Decreased in Healthy Subjects After a Long Period of Time

et al. 2008

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The stability of bile acid turnover rate was evaluated retrospectively using repeat SeHCAT tests in patients with chronic diarrhoea and prospectively for 16 years in healthy subjects. The SeHCAT values were stable in 39 patients with chronic diarrhoea, as shown by a comparison of the test results [data presented as median and (25th-75th percentile)]: 18% (8-23) in the first test versus 14% (9-21) in the second test [n = 39, P = 0.37, time interval 44 months (16-68), repeatability index >95%]. In contrast, they were reduced after 16 years in healthy subjects: 38% (30-49.5) in the first test versus 31% (21-49.5) in the second test (P < 0.03). In healthy subjects, the body mass index increased by 13% from 23.2 kg/m(2) (21-24.6) to 26.2 kg/m(2) (22.5-27.8) (P < 0.01) during the 16 years. There was a negative correlation between hepatic bile acid synthesis and the SeHCAT values (r = -0.615, P = 0.02, n = 14). In conclusion, the turnover rate of bile acids is stable over a long period of time in patients with chronic diarrhoea irrespective of bile acid malabsorption, suggesting that a repeat SeHCAT test is dispensable. There is a significant negative correlation between bile acid synthesis and SeHCAT test results in healthy subjects. The SeHCAT test values are slightly reduced in healthy subjects after 16 years.

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Age‐related changes in bile acid synthesis and hepatic nuclear receptor expression

Cited by 59 publications

References 47 publications

Mathematically modelling the dynamics of cholesterol metabolism and ageing

Mathematically modelling the dynamics of cholesterol metabolism and ageing

Investigating cholesterol metabolism and ageing using a systems biology approach

The Bile Acid Turnover Rate Assessed with the 75SeHCAT Test Is Stable in Chronic Diarrhoea but Slightly Decreased in Healthy Subjects After a Long Period of Time

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