Mice, Inbred C57BL

Publication Title: 
Diabetologia

AIMS/HYPOTHESIS: Sirtuin 1 (SIRT1) is a longevity-associated protein, which regulates energy metabolism and lifespan in response to nutrient deprivation. It has been proposed to be a therapeutic target for obesity and metabolic syndrome. We investigated whether ?-lipoic acid (ALA) exerts a lipid-lowering effect through regulation of SIRT1 activation and production in C(2)C(12) myotubes.

Author(s): 
Chen, W.-L.
Kang, C.-H.
Wang, S.-G.
Lee, H.-M.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Dietary interventions are effective ways to extend or shorten lifespan. By examining midlife hepatic gene expressions in mice under different dietary conditions, which resulted in different lifespans and aging-related phenotypes, we were able to identify genes and pathways that modulate the aging process. We found that pathways transcriptionally correlated with diet-modulated lifespan and physiological changes were enriched for lifespan-modifying genes.

Author(s): 
Zhou, Bing
Yang, Liu
Li, Shoufeng
Huang, Jialiang
Chen, Haiyang
Hou, Lei
Wang, Jinbo
Green, Christopher D.
Yan, Zhen
Huang, Xun
Kaeberlein, Matt
Zhu, Li
Xiao, Huasheng
Liu, Yong
Han, Jing-Dong J.
Publication Title: 
Cell Stem Cell

Calorie restriction (CR) extends life span and ameliorates age-related pathologies in most species studied, yet the mechanisms underlying these effects remain unclear. Using mouse skeletal muscle as a model, we show that CR acts in part by enhancing the function of tissue-specific stem cells. Even short-term CR significantly enhanced stem cell availability and activity in the muscle of young and old animals, in concert with an increase in mitochondrial abundance and induction of conserved metabolic and longevity regulators.

Author(s): 
Cerletti, Massimiliano
Jang, Young C.
Finley, Lydia W. S.
Haigis, Marcia C.
Wagers, Amy J.
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Because rapamycin, an inhibitor of the nutrient sensor mammalian target of rapamycin, and dietary restriction both increase life span of mice, it has been hypothesized that they act through similar mechanisms. To test this hypothesis, we compared various biological parameters in dietary restriction mice (40% food restriction) and mice fed rapamycin (14 ppm). Both treatments led to a significant reduction in mammalian target of rapamycin signaling and a corresponding increase in autophagy.

Author(s): 
Fok, Wilson C.
Zhang, Yiqiang
Salmon, Adam B.
Bhattacharya, Arunabh
Gunda, Rakesh
Jones, Dean
Ward, Walter
Fisher, Kathleen
Richardson, Arlan
PÈrez, Viviana I.
Publication Title: 
American Journal of Physiology. Endocrinology and Metabolism

Xenobiotic metabolism has been proposed to play a role in modulating the rate of aging. Xenobiotic metabolizing enzymes (XME) are expressed at higher levels in calorically restricted mice (CR) and in GH/IGF-I-deficient, long-lived mutant mice. In this study, we show that many phase I XME genes are similarly upregulated in additional long-lived mouse models, including "crowded litter" (CL) mice, whose lifespan has been increased by food restriction limited to the first 3 wk of life, and in mice treated with rapamycin.

Author(s): 
Steinbaugh, Michael J.
Sun, Liou Y.
Bartke, Andrzej
Miller, Richard A.
Publication Title: 
Molecular & cellular proteomics: MCP

Calorie restriction (CR) promotes longevity. A prevalent mechanistic hypothesis explaining this effect suggests that protein degradation, including mitochondrial autophagy, is increased with CR, removing damaged proteins and improving cellular fitness. At steady state, increased catabolism must be balanced by increasing mitochondrial biogenesis and protein synthesis, resulting in faster protein replacement rates.

Author(s): 
Price, John C.
Khambatta, Cyrus F.
Li, Kelvin W.
Bruss, Matthew D.
Shankaran, Mahalakshmi
Dalidd, Marcy
Floreani, Nicholas A.
Roberts, Lindsay S.
Turner, Scott M.
Holmes, William E.
Hellerstein, Marc K.
Publication Title: 
PloS One

BACKGROUND: Glioma, including anaplastic astrocytoma and glioblastoma multiforme (GBM) are among the most commonly diagnosed malignant adult brain tumors. GBM is a highly invasive and angiogenic tumor, resulting in a 12 to 15 months median survival. The treatment of GBM is multimodal and includes surgical resection, followed by adjuvant radio-and chemotherapy. We have previously reported that short-term starvation (STS) enhances the therapeutic index of chemo-treatments by differentially protecting normal cells against and/or sensitizing tumor cells to chemotoxicity.

Author(s): 
Safdie, Fernando
Brandhorst, Sebastian
Wei, Min
Wang, Weijun
Lee, Changhan
Hwang, Saewon
Conti, Peter S.
Chen, Thomas C.
Longo, Valter D.
Publication Title: 
International Journal of Obesity (2005)

OBJECTIVE: With the increasing rates of obesity, many people diet in an attempt to lose weight. As weight loss is seldom maintained in a single effort, weight cycling is a common occurrence. Unfortunately, reports from clinical studies that have attempted to determine the effect of weight cycling on mortality are in disagreement, and to date, no controlled animal study has been performed to assess the impact of weight cycling on longevity.

Author(s): 
List, E. O.
Berryman, D. E.
Wright-Piekarski, J.
Jara, A.
Funk, K.
Kopchick, J. J.
Publication Title: 
American Journal of Physiology. Endocrinology and Metabolism

Ectopic expression of uncoupling protein 1 (UCP1) in skeletal muscle (SM) mitochondria increases lifespan considerably in high-fat diet-fed UCP1 Tg mice compared with wild types (WT). To clarify the underlying mechanisms, we investigated substrate metabolism as well as oxidative stress damage and antioxidant defense in SM of low-fat- and high-fat-fed mice. Tg mice showed an increased protein expression of phosphorylated AMP-activated protein kinase, markers of lipid turnover (p-ACC, FAT/CD36), and an increased SM ex vivo fatty acid oxidation.

Author(s): 
Keipert, S.
Ost, M.
Chadt, A.
Voigt, A.
Ayala, V.
Portero-Otin, M.
Pamplona, R.
Al-Hasani, H.
Klaus, S.
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.

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