Intestines

Publication Title: 
Cancer Research

C57BL/6J mice carrying the Min allele of Adenomatous polyposis coli (Apc) develop numerous adenomas along the entire length of the intestine and consequently die at an early age. This short lifespan would prevent the accumulation of somatic genetic mutations or epigenetic alterations necessary for tumor progression. To overcome this limitation, we generated F(1) Apc(Min/+) hybrids by crossing C57BR/cdcJ and SWR/J females to C57BL/6J Apc(Min/+) males. These hybrids developed few intestinal tumors and often lived longer than 1 year.

Author(s): 
Halberg, Richard B.
Waggoner, Jesse
Rasmussen, Kristen
White, Alanna
Clipson, Linda
Prunuske, Amy J.
Bacher, Jeffery W.
Sullivan, Ruth
Washington, Mary Kay
Pitot, Henry C.
Petrini, John H. J.
Albertson, Donna G.
Dove, William F.
Publication Title: 
Ageing Research Reviews

Multicellular organisms are composed of an interactive network of various tissues that are functionally organized as discrete organs. If aging were slowed in a specific tissue or organ how would that impact longevity at the organismal level? In recent years, molecular genetic approaches in invertebrate model systems have dramatically improved our understanding of the aging process and have provided insight into the preceding question.

Author(s): 
Rera, Michael
Azizi, Masoud J.
Walker, David W.
Publication Title: 
Cell

Both poikilotherms and homeotherms live longer at lower body temperatures, highlighting a general role of temperature reduction in lifespan extension. However, the underlying mechanisms remain unclear. One prominent model is that cold temperatures reduce the rate of chemical reactions, thereby slowing the rate of aging. This view suggests that cold-dependent lifespan extension is simply a passive thermodynamic process. Here, we challenge this view in C. elegans by showing that genetic programs actively promote longevity at cold temperatures.

Author(s): 
Xiao, Rui
Zhang, Bi
Dong, Yongming
Gong, Jianke
Xu, Tao
Liu, Jianfeng
Xu, X. Z. Shawn
Publication Title: 
PloS One

The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-?-carboline) increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin-producing Escherichia coli O157:H7 strain EDL933 and several other bacterial pathogens. This was shown to be unrelated to the weak antibiotic effect of Harmane. Using GFP-expressing E. coli EDL933, we showed that Harmane does not lower the colonization burden in the nematodes.

Author(s): 
Jakobsen, Henrik
Bojer, Martin S.
Marinus, Martin G.
Xu, Tao
Struve, Carsten
Krogfelt, Karen A.
L¯bner-Olesen, Anders
Publication Title: 
Ageing Research Reviews

Multicellular organisms are composed of an interactive network of various tissues that are functionally organized as discrete organs. If aging were slowed in a specific tissue or organ how would that impact longevity at the organismal level? In recent years, molecular genetic approaches in invertebrate model systems have dramatically improved our understanding of the aging process and have provided insight into the preceding question.

Author(s): 
Rera, Michael
Azizi, Masoud J.
Walker, David W.
Publication Title: 
PloS One

BACKGROUND: Zinc deficiency due to poor nutrition or genetic mutations in zinc transporters is a global health problem and approaches to providing effective dietary zinc supplementation while avoiding potential toxic side effects are needed. METHODS/PRINCIPAL FINDINGS: Conditional knockout of the intestinal zinc transporter Zip4 (Slc39a4) in mice creates a model of the lethal human genetic disease acrodermatitis enteropathica (AE).

Author(s): 
Geiser, Jim
De Lisle, Robert C.
Finkelstein, David
Adlard, Paul A.
Bush, Ashley I.
Andrews, Glen K.
Publication Title: 
Nature Chemical Biology

Gut microbiota is found in virtually any metazoan, from invertebrates to vertebrates. It has long been believed that gut microbiota, more specifically, the activity of the microbiome and its metabolic products, directly influence a variety of aspects in metazoan physiology. However, the exact molecular relationship among microbe-derived gut metabolites, host signaling pathways, and host physiology remains to be elucidated. Here we review recent discoveries regarding the molecular links between gut metabolites and host physiology in different invertebrate and vertebrate animal models.

Author(s): 
Lee, Won-Jae
Hase, Koji
Publication Title: 
Frontiers in Bioscience: A Journal and Virtual Library

The incidence of intestinal nutrient malabsorption increases with age. Therefore, an important question is whether there are age-related changes in intestinal nutrient absorption which may contribute to a decline in absorptive capacity. Sugar and amino acid transport per mg intestine generally decreases with age. The proximate mechanism underlying this age-related decrease in transport activity is a decrease in number of transporters per mg.

Author(s): 
Ferraris, R. P.
Publication Title: 
PloS One

BACKGROUND: In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced body weight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. Alteration in the liver gene expression profile, in behavior and metabolism point to a calorie restriction-like phenotype in Eps8 knockout mice.

Author(s): 
Tocchetti, Arianna
Soppo, Charlotte Blanche Ekalle
Zani, Fabio
Bianchi, Fabrizio
Gagliani, Maria Cristina
Pozzi, Benedetta
Rozman, Jan
Elvert, Ralf
Ehrhardt, Nicole
Rathkolb, Birgit
Moerth, Corinna
Horsch, Marion
Fuchs, Helmut
Gailus-Durner, ValÈrie
Beckers, Johannes
Klingenspor, Martin
Wolf, Eckhard
HrabÈ de Angelis, Martin
Scanziani, Eugenio
Tacchetti, Carlo
Scita, Giorgio
Di Fiore, Pier Paolo
Offenh‰user, Nina
Publication Title: 
Nature

How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin.

Author(s): 
Yilmaz, ÷mer H.
Katajisto, Pekka
Lamming, Dudley W.
G¸ltekin, Yetis
Bauer-Rowe, Khristian E.
Sengupta, Shomit
Birsoy, Kivanc
Dursun, Abdulmetin
Yilmaz, V. Onur
Selig, Martin
Nielsen, G. Petur
Mino-Kenudson, Mari
Zukerberg, Lawrence R.
Bhan, Atul K.
Deshpande, Vikram
Sabatini, David M.

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