Mice

Publication Title: 
Human Molecular Genetics

Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. SMA is caused by loss of functional survival motor neuron 1 (SMN1), resulting in death of spinal motor neurons. Current therapeutic research focuses on modulating the expression of a partially functioning copy gene, SMN2, which is retained in SMA patients. However, a treatment strategy that improves the SMA phenotype by slowing or reversing the skeletal muscle atrophy may also be beneficial. Myostatin, a member of the TGF-beta super-family, is a potent negative regulator of skeletal muscle mass.

Author(s): 
Rose, Ferrill F.
Mattis, Virginia B.
Rindt, Hansjˆrg
Lorson, Christian L.
Publication Title: 
Experimental & Molecular Medicine

Neural progenitor cells (NPs) have shown several promising benefits for the treatment of neurological disorders. To evaluate the therapeutic potential of human neural progenitor cells (hNPs) in amyotrophic lateral sclerosis (ALS), we transplanted hNPs or growth factor (GF)-expressing hNPs into the central nervous system (CNS) of mutant Cu/Zn superoxide dismutase (SOD1(G93A)) transgenic mice.

Author(s): 
Park, Sungju
Kim, Hyoung-Tae
Yun, Seokkwan
Kim, Il-Sun
Lee, Jiyoon
Lee, Il-Shin
Park, Kook In
Publication Title: 
Aging Cell

Major advances in aging research have been made by studying the effect of genetic modifications on the lifespan of organisms, such as yeast, invertebrates (worms and flies) and mice. Data from yeast and invertebrates have been the most plentiful because of the ease in which genetic manipulations can be made and the rapidity by which lifespan experiments can be performed. With the ultimate focus on advancing human health, testing genetic interventions in mammals is crucial, and the mouse has proven to be the mammal most amenable to this task.

Author(s): 
Ladiges, Warren
Van Remmen, Holly
Strong, Randy
Ikeno, Yuji
Treuting, Piper
Rabinovitch, Peter
Richardson, Arlan
Publication Title: 
Biochimica Et Biophysica Acta

Studies in a variety of model organisms indicate that nutrient signaling is tightly coupled to longevity. In nutrient replete conditions, organisms develop, grow, and age quickly. When nutrients become sparse as with dietary restriction, growth and development decline, stress response pathways become induced and organisms live longer. Considerable effort has been devoted to understanding the molecular events mediating lifespan extension by dietary restriction.

Author(s): 
Stanfel, Monique N.
Shamieh, Lara S.
Kaeberlein, Matt
Kennedy, Brian K.
Publication Title: 
Aging Cell

This annual review focuses on invertebrate model organisms, which shed light on new mechanisms in aging and provide excellent systems for both genome-wide and in-depth analysis. This year, protein interaction networks have been used in a new bioinformatic approach to identify novel genes that extend replicative lifespan in yeast. In an extended approach, using a new, human protein interaction network, information from the invertebrates was used to identify new, candidate genes for lifespan extension and their orthologues were validated in the nematode Caenorhabditis elegans.

Author(s): 
Partridge, Linda
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: 
Nature Chemical Biology

Cellular damage invoked by reactive oxygen species plays a key role in the pathobiology of cancer and aging. Forkhead box class O (FoxO) transcription factors are involved in various cellular processes including cell cycle regulation, apoptosis and resistance to reactive oxygen species, and studies in animal models have shown that these transcription factors are of vital importance in tumor suppression, stem cell maintenance and lifespan extension.

Author(s): 
Dansen, Tobias B.
Smits, Lydia M. M.
van Triest, Miranda H.
de Keizer, Peter L. J.
van Leenen, Dik
Koerkamp, Marian Groot
Szypowska, Anna
Meppelink, Amanda
Brenkman, Arjan B.
Yodoi, Junji
Holstege, Frank C. P.
Burgering, Boudewijn M. T.
Publication Title: 
Aging Cell

Significant extension of lifespan in important mammalian species is bound to attract the attention not only of the aging research community, but also the media and the wider public. Two recent papers published by Harrison et al. (2009) in Nature and by Colman et al. (2009) in Science report increased longevity of mice fed with rapamycin and of rhesus monkeys undergoing caloric restriction, respectively. These papers have generated considerable debate in the aging community.

Author(s): 
Cox, Lynne S.
Mattison, Julie A.
Publication Title: 
Rejuvenation Research

Can we extend human lifespan? Do we need to regulate lifestyle choices or can we simply pop a pill to make us live longer? These are questions raised by two new studies demonstrating significant lifespan extension in mice fed the drug rapamycin in their diet and in calorically restricted rhesus monkeys.

Author(s): 
Cox, Lynne S.
Publication Title: 
Molecular Therapy: The Journal of the American Society of Gene Therapy

Methylmalonic acidemia (MMA) is an organic acidemia caused by deficient activity of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT). This disorder is associated with lethal metabolic instability and carries a poor prognosis for long-term survival. A murine model of MMA that replicates a severe clinical phenotype was used to examine the efficacy of recombinant adeno-associated virus (rAAV) serotype 8 gene therapy as a treatment for MMA.

Author(s): 
Chandler, Randy J.
Venditti, Charles P.

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