Mice, Inbred C57BL

Publication Title: 
MÈdecine Sciences: M/S

Most of the signalling pathways involved in aging regulation have been recently found well conserved at various levels throughout the evolution. Taking this into account, a diversity of model organisms, including worms, rodents, and lemurs as well, allows to address different questions: how to understand the interactions between genetic and environmental factors while challenging theories of aging, to preserve hearing integrity, to fight against senescence of neural stem cells, or to explore brain fitness from gene expression to cognitive and social behavior?

Author(s): 
Galas, Simon
Ch‚teau, Marie-ThÈrËse
PomiËs, Pascal
Wang, Jing
Menardo, Julien
Puel, Jean-Luc
Hugnot, Jean-Philippe
Verdier, Jean-Michel
Devau, Gina
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Quantitative trait loci (QTL) of longevity identified in human and mouse are significantly colocalized, suggesting that common mechanisms are involved. However, the limited number of strains that have been used in mouse longevity studies undermines the ability to identify longevity genes. We crossed C57BL/6J mice with a new wild-derived strain, Pohn, and identified two life span QTL-Ls1 and Ls2. Interestingly, homologous human longevity QTL colocalize with Ls1. We also defined new QTL for metabolic heat production and body weight.

Author(s): 
Yuan, Rong
Flurkey, Kevin
Meng, Qingying
Astle, Mike C.
Harrison, David E.
Publication Title: 
Human Molecular Genetics

The CISD2 gene, which is an evolutionarily conserved novel gene, encodes a transmembrane protein primarily associated with the mitochondrial outer membrane. Significantly, the CISD2 gene is located within the candidate region on chromosome 4q where a genetic component for human longevity has been mapped. Previously, we have shown that Cisd2 deficiency shortens lifespan resulting in premature aging in mice. Additionally, an age-dependent decrease in Cisd2 expression has been detected during normal aging.

Author(s): 
Wu, Chia-Yu
Chen, Yi-Fan
Wang, Chih-Hao
Kao, Cheng-Heng
Zhuang, Hui-Wen
Chen, Chih-Cheng
Chen, Liang-Kung
Kirby, Ralph
Wei, Yau-Huei
Tsai, Shih-Feng
Tsai, Ting-Fen
Publication Title: 
Blood

Although the overproduction of immunoglobulins by short-lived plasma cells accompanying an immune response links with their apoptosis, how long-lived plasma cells adapt to ensure their longevity in this context is obscure. Here, we show that apoptosis signal-regulating kinase 1 (ASK1) contributes to apoptosis of plasma cells because ASK1 activity was induced during differentiation of short-lived plasma cells, and, when produced by ASK1-deficient mice, these cells survived better than those of control mice.

Author(s): 
Lin, Fan-Ru
Huang, Shang-Yi
Hung, Kuo-Hsuan
Su, Shin-Tang
Chung, Cheng-Han
Matsuzawa, Atsushi
Hsiao, Michael
Ichijo, Hidenori
Lin, Kuo-I.
Publication Title: 
Cell Reports

Aberrantly short telomeres result in decreased longevity in both humans and mice with defective telomere maintenance. Normal populations of humans and mice present high interindividual variation in telomere length, but it is unknown whether this is associated with their lifespan potential. To address this issue, we performed a longitudinal telomere length study along the lifespan of wild-type and transgenic telomerase reverse transcriptase mice. We found that mouse telomeres shorten ?100 times faster than human telomeres.

Author(s): 
Vera, Elsa
Bernardes de Jesus, Bruno
Foronda, Miguel
Flores, Juana M.
Blasco, Maria A.
Publication Title: 
Neuromolecular Medicine

A common cause of amyotrophic lateral sclerosis is mutations in superoxide dismutase-1, which provoke the disease by an unknown mechanism. We have previously found that soluble hydrophobic misfolded mutant human superoxide dismutase-1 species are enriched in the vulnerable spinal cords of transgenic model mice. The levels were broadly inversely correlated with life spans, suggesting involvement in the pathogenesis.

Author(s): 
Zetterstrˆm, Per
Graffmo, Karin S.
Andersen, Peter M.
Br‰nnstrˆm, Thomas
Marklund, Stefan L.
Publication Title: 
Cellular and molecular life sciences: CMLS

Reduction of nutrient intake without malnutrition positively influences lifespan and healthspan from yeast to mice and exerts some beneficial effects also in humans. The AMPK-FoxO axis is one of the evolutionarily conserved nutrient-sensing pathways, and the FOXO3A locus is associated with human longevity. Interestingly, FoxO3A has been reported to be also a mitochondrial protein in mammalian cells and tissues. Here we report that glucose restriction triggers FoxO3A accumulation into mitochondria of fibroblasts and skeletal myotubes in an AMPK-dependent manner.

Author(s): 
Peserico, Alessia
Chiacchiera, Fulvio
Grossi, Valentina
Matrone, Antonio
Latorre, Dominga
Simonatto, Marta
Fusella, Aurora
Ryall, James G.
Finley, Lydia W. S.
Haigis, Marcia C.
Villani, Gaetano
Puri, Pier Lorenzo
Sartorelli, Vittorio
Simone, Cristiano
Publication Title: 
Cell Death and Differentiation

Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition with no cure. Mitochondrial dysfunction, Ca(2+) overloading and local hypoxic/ischemic environments have been implicated in the pathophysiology of ALS and are conditions that may initiate metabolic acidosis in the affected tissue. We tested the hypothesis that acidotoxicity and acid-sensing ion channels (ASICs) are involved in the pathophysiology of ALS. We found that motoneurons were selectively vulnerable to acidotoxicity in vitro, and that acidotoxicity was partially reduced in asic1a-deficient motoneuron cultures.

Author(s): 
Behan, A. T.
Breen, B.
Hogg, M.
Woods, I.
Coughlan, K.
Mitchem, M.
Prehn, J. H. M.
Publication Title: 
PloS One

Caloric restriction (CR), a reduction of food intake while avoiding malnutrition, can delay the onset of cancer and age-related diseases in several species, including mice. In addition, depending of the genetic background, CR can also increase or decrease mouse longevity. This has highlighted the importance of identifying the molecular pathways that interplay with CR in modulating longevity. Significant lifespan extension in mice has been recently achieved through over-expression of the catalytic subunit of mouse telomerase (mTERT) in a cancer protective background.

Author(s): 
Vera, Elsa
Bernardes de Jesus, Bruno
Foronda, Miguel
Flores, Juana M.
Blasco, Maria A.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Tumors use a wide array of immunosuppressive strategies, such as reducing the longevity and survival of dendritic cells (DCs), to diminish immune responses and limit the effect of immunotherapy. In this study, we found that tumors upregulate the expression of multiple microRNAs (miRNAs), such as miR-16-1, miR-22, miR-155, and miR-503. These tumor-associated miRNAs influenced the survival and longevity of DCs by affecting the expression of multiple molecules that are associated with apoptotic signaling pathways.

Author(s): 
Min, Siping
Liang, Xue
Zhang, Miaomiao
Zhang, Yuan
Mei, Shiyue
Liu, Jinzhe
Liu, Jingyi
Su, Xiaomin
Cao, Shuisong
Zhong, Xueqing
Li, Yueming
Sun, Jiatan
Liu, Qiaofei
Jiang, Xingran
Che, Yongzhe
Yang, Rongcun

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