Mice

Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

In investigating the role of metal ions in the pathogenesis of Huntington's disease, we examined the effects of clioquinol, a metal-binding compound currently in clinical trials for Alzheimer's disease treatment, on mutant huntingtin-expressing cells. We found that PC12 cells expressing polyglutamine-expanded huntingtin exon 1 accumulated less mutant protein and showed decreased cell death when treated with clioquinol. This effect was polyglutamine-length-specific and did not alter mRNA levels or protein degradation rates.

Author(s): 
Nguyen, Trent
Hamby, Aaron
Massa, Stephen M.
Publication Title: 
Experimental Gerontology

The purpose of this brief review is to highlight some of the more important advances in endocrinology of aging research over the past year. Four advances were chosen and briefly described.

Author(s): 
Bellino, Francis L.
Publication Title: 
Nature

XPF-ERCC1 endonuclease is required for repair of helix-distorting DNA lesions and cytotoxic DNA interstrand crosslinks. Mild mutations in XPF cause the cancer-prone syndrome xeroderma pigmentosum. A patient presented with a severe XPF mutation leading to profound crosslink sensitivity and dramatic progeroid symptoms. It is not known how unrepaired DNA damage accelerates ageing or its relevance to natural ageing. Here we show a highly significant correlation between the liver transcriptome of old mice and a mouse model of this progeroid syndrome.

Author(s): 
Niedernhofer, Laura J.
Garinis, George A.
Raams, Anja
Lalai, Astrid S.
Robinson, Andria Rasile
Appeldoorn, Esther
Odijk, Hanny
Oostendorp, Roos
Ahmad, Anwaar
van Leeuwen, Wibeke
Theil, Arjan F.
Vermeulen, Wim
van der Horst, Gijsbertus T. J.
Meinecke, Peter
Kleijer, Wim J.
Vijg, Jan
Jaspers, Nicolaas G. J.
Hoeijmakers, Jan H. J.
Publication Title: 
Journal of the Neurological Sciences

Amyotrophic lateral sclerosis (ALS) is a progressive disease which is caused by degeneration of motor neurons in the central nervous system. The incidence of ALS is higher in men than women, but the female advantage disappears with increased age. Here, we report evidence that the female advantage is due to the protective role of estrogen. In an ALS mouse model carrying the human Cu/Zn superoxide dismutase (hSOD1) G93A transgene, ovariectomy did not alter the onset age of the disease while reducing the female lifespan by 7 days and making it comparable to that of the male transgenic mice.

Author(s): 
Choi, Chan-Il
Lee, Young-Don
Gwag, Byoung Joo
Cho, Sung Ig
Kim, Sung-Soo
Suh-Kim, Haeyoung
Publication Title: 
Acta Physiologica (Oxford, England)

Ageing is associated with an increased onset of cancer. Understanding the molecular mechanisms that underlie the age dependency of cancer will have important implications for preventing and treating this pathology. The signalling pathway connecting insulin and FOXO transcription factors provides the most compelling example for a conserved genetic pathway at the interface between ageing and cancer. FOXO transcription factors (FOXO) promote longevity and tumour suppression.

Author(s): 
Greer, E. L.
Brunet, A.
Publication Title: 
Cell Cycle (Georgetown, Tex.)

Genetic studies in model organisms such as yeast, worms, flies, and mice leading to lifespan extension suggest that longevity is subject to regulation. In addition, various system-wide interventions in old animals can reverse features of aging. To better understand these processes, much effort has been put into the study of aging on a molecular level. In particular, genome-wide microarray analysis of differently aged individual organisms or tissues has been used to track the global expression changes that occur during normal aging.

Author(s): 
Adler, Adam S.
Kawahara, Tiara L. A.
Segal, Eran
Chang, Howard Y.
Publication Title: 
Human Molecular Genetics

Autophagy is a highly regulated intracellular process involved in the turnover of most cellular constituents and in the maintenance of cellular homeostasis. It is well-established that the basal autophagic activity of living cells decreases with age, thus contributing to the accumulation of damaged macromolecules during aging. Conversely, the activity of this catabolic pathway is required for lifespan extension in animal models such as Caenorhabditis elegans and Drosophila melanogaster.

Author(s): 
MariÒo, Guillermo
Ugalde, Alejandro P.
Salvador-Montoliu, Natalia
Varela, Ignacio
QuirÛs, Pedro M.
CadiÒanos, Juan
van der Pluijm, Ingrid
Freije, JosÈ M. P.
LÛpez-OtÌn, Carlos
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

The burden of protein misfolding is believed to contribute to aging. However, the links between adaptations to conditions associated with protein misfolding and resistance to the time-dependent attrition of cellular function remain poorly understood. We report that worms lacking aip-1, a homologue of mammalian AIRAP (arsenic-inducible proteasomal 19S regulatory particle-associated protein), are not only impaired in their ability to resist exposure to arsenite but also exhibit shortened lifespan and hypersensitivity to misfolding-prone proteins under normal laboratory conditions.

Author(s): 
Yun, Chi
Stanhill, Ariel
Yang, Yun
Zhang, Yuhong
Haynes, Cole M.
Xu, Chong-Feng
Neubert, Thomas A.
Mor, Adam
Philips, Mark R.
Ron, David
Publication Title: 
PLoS genetics

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan. Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice.

Author(s): 
Schumacher, Bjˆrn
van der Pluijm, Ingrid
Moorhouse, Michael J.
Kosteas, Theodore
Robinson, Andria Rasile
Suh, Yousin
Breit, Timo M.
van Steeg, Harry
Niedernhofer, Laura J.
van Ijcken, Wilfred
Bartke, Andrzej
Spindler, Stephen R.
Hoeijmakers, Jan H. J.
van der Horst, Gijsbertus T. J.
Garinis, George A.
Publication Title: 
Medical Hypotheses

Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving "aging retardant" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid.

Author(s): 
McCarty, Mark F.
Barroso-Aranda, Jorge
Contreras, Francisco

Pages

Subscribe to RSS - Mice