Caloric restriction improves thermotolerance and reduces hyperthermia‐induced cellular damage in old rats

Huang

The American Journal of Pathology

et al. 2004

105

Hepatic polycystic disease occurs alone or in combination with polycystic kidney disease (PKD). In autosomal recessive PKD (ARPKD), liver lesions are the major cause of morbidity and mortality in older patients. ARPKD is caused by a mutation to PKHD1 and the PCK rat is an orthologous model of disease. Recently, we showed that fibrocystin, Pkhd1 protein, is localized to primary cilia in rat cholangiocytes and that disruption of its ciliary expression results in biliary cystogenesis. This study describes biliary phenotype in the PCK rat using micro-computed tomography scanning and three-dimensional reconstruction, and light, scanning, and transmission microscopy. Our results show that the biliary tree undergoes extensive remodeling resulting in bile duct dilatation, focal budding, and formation of cysts that are initially connected to bile ducts, but throughout time separate from them. Progressive liver enlargement results from massive cyst formation while liver parenchymal volume remains unchanged. Cilia in cystic cells are abnormal consistent with the notion that the primary defect in ARPKD resulting in cystogenesis may be linked to ciliary dysfunction. Our results suggest that the PCK rat is a useful model for studies of biliary cystogenesis and treatment options of inherited cystic liver disease.

Section: Animals and Experimental Modelsmentioning

confidence: 75%

Section: Gross Anatomy and Liver Pathologymentioning

confidence: 99%

Biliary Dysgenesis in the PCK Rat, an Orthologous Model of Autosomal Recessive Polycystic Kidney Disease

Huang

The American Journal of Pathology

et al. 2004

105

Ageing Research Reviews

“…For example, mortality from natural causes or that caused by thermal and oxidative stress exposures to specific toxins is significantly reduced in animals that have been maintained on DER compared to control animals consuming a normal diet (Fernandes et al, 1976;Hall et al, 2000;Vasselli et al, 2005;Lee et al, 2006). DER protects rodents against cancers induced in a wide range of tissues and by many different carcinogens including pancreatic tumors induced by azaserine (Roebuck et al, 1981), mammary tumors induced by DMBA (Klurfeld et al, 1989) and prostate cancer induced by N-methyl-N-nitrosourea and testosterone (Boileau et al, 2003).…”

Section: Dietary Energy Intake and Hormesismentioning

confidence: 99%

Dietary factors, hormesis and health

Mattson¹

2008

257

180

The impact of dietary factors on health and longevity is increasingly appreciated. The most prominent dietary factor that affects the risk of many different chronic diseases is energy intake -excessive calorie intake increases the risk. Reducing energy intake by controlled caloric restriction or intermittent fasting increases lifespan and protects various tissues against disease, in part, by hormesis mechanisms that increase cellular stress resistance. Some specific dietary components may also exert health benefits by inducing adaptive cellular stress responses. Indeed, recent findings suggest that several heavily studied phytochemicals exhibit biphasic dose responses on cells with low doses activating signaling pathways that result in increased expression of genes encoding cytoprotective proteins including antioxidant enzymes, protein chaperones, growth factors and mitochondrial proteins. Examples include: activation of the Nrf-2 -ARE pathway by sulforaphane and curcumin; activation of TRP ion channels by allicin and capsaicin; and activation of sirtuin-1 by resveratrol. Research that establishes dose response and kinetic characteristics of the effects of dietary factors on cells, animals and humans will lead to a better understanding of hormesis and to improvements in dietary interventions for disease prevention and treatment.

American Journal of Physiology-Endocrinology and Metabolism

“…In particular, the details of the response of cell proliferation to CR, including the time course, dose-response relationships, effects of refeeding, and endocrine correlations, have not been established. The effect of using different control groups in the CR field [e.g., AL vs. 5-15% restriction (1,5,13,23,24,37,41,43,44,46)] also has not been systematically explored. Finally, intermittency of feeding of both controls and CR models also has varied in the field (13,23,37,42,46) and could influence the effects of CR on cell proliferation.…”

mentioning

confidence: 99%

Effects of caloric restriction on cell proliferation in several tissues in mice: role of intermittent feeding

Hsieh¹,

Chai²,

Hellerstein³

2005

Reduced cell proliferation may mediate anticarcinogenic effects of caloric restriction (CR). Using heavy water ( 2 H2O) labeling, we investigated the cell proliferation response to CR in detail, including time course, effect of refeeding, and role of intermittent feeding with 5% CR. In the time-course study, 8-wk-old female C57BL/6J mice were placed on a 33% CR regimen (fed 3 times/wk) for varying durations. Compared with responses in controls fed ad libitum (AL), proliferation rates of keratinocytes, mammary epithelial cells, and T cells were markedly reduced within 2 wk of CR. In mice fed 95% ad libitum (C95, fed 3 times/wk), cell proliferation was also reduced in all tissues so that differences from 33% CR were only significant at 1 mo. In the refeeding study, mice were refed a C95 diet for varying durations after 1 mo of 33% CR. Cell proliferation rebounded to a suprabasal rate in all tissues after 2 wk of refeeding and then normalized after 2 mo, although the C95 group again exhibited lower cell proliferation than the AL group. The role of intermittent feeding was studied by comparing 33% CR and C95 animals (both fed intermittently) with animals fed isocalorically either daily or continuously by pellet dispenser. Intermittent feeding had no additive effect on 33% CR but reduced cell proliferation in all tissues at the 95% caloric intake level. In summary, the CR effect on cell proliferation is potent, rapid, and reversible in several tissues, and an intermittent feeding pattern reproduces much of the effect in the absence of substantial CR. stable isotopes; refeeding; keratinocyte; mammary; T cell CALORIC RESTRICTION (CR), defined as undernutrition without malnutrition (45), was first discovered in 1935 to extend maximal life span in rats (29). Since then, similar findings have been reported in mice, fish, flies, worms, and yeast (45). A range of 30 -70% extension of maximal life span has been achieved using variations on CR regimens (45), including both early-and adult-onset CR (44,46). CR also exerts a number of other beneficial health effects, including reduced carcinogenesis, enhanced insulin sensitivity, and reduced cardiovascular disease risk (15). The inhibitory effect of CR on carcinogenesis is of particular interest, because CR effectively inhibits spontaneous tumor formation as well as neoplasias in knockout/ transgenic models of cancer-and chemically induced tumorigenesis (18,19,45). The mechanisms by which CR extends life span and inhibits carcinogenesis remain unknown (15,19).CR could affect several steps in the multistage carcinogenesis model (18). CR may function as an anti-initiator by decreasing carcinogen activation, enhancing carcinogen detoxification, scavenging reactive oxygen species, or enhancing DNA repair (18). CR could also function as an antipromoter by reducing mitoses of initiated cells, altering expression of cancer-related genes, decreasing inflammation, enhancing immune competence, or stimulating apoptosis (18). Reductions in cell proliferation might be expected in view of ob...