Mice, Inbred C57BL

Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

We analyzed ultrastructural changes and markers of fission/fusion in hepatocyte mitochondria from mice submitted to 40% calorie restriction (CR) for 6 months versus ad-libitum-fed controls. To study the effects of dietary fat under CR, animals were separated into three CR groups with soybean oil (also in controls), fish oil, and lard. CR induced differential changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte.

Author(s): 
Khraiwesh, Husam
LÛpez-DomÌnguez, JosÈ A.
LÛpez-Lluch, Guillermo
Navas, Pl·cido
de Cabo, Rafael
Ramsey, Jon J.
Villalba, JosÈ M.
Gonz·lez-Reyes, JosÈ A.
Publication Title: 
Aging Cell

Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, extends the life span of yeast, worms, flies, and mice. Interventions that promote longevity are often correlated with increased insulin sensitivity, and it therefore is surprising that chronic rapamycin treatment of mice, rats, and humans is associated with insulin resistance (J Am Soc Nephrol., 19, 2008, 1411; Diabetes, 00, 2010, 00; Science, 335, 2012, 1638).

Author(s): 
Lamming, Dudley W.
Ye, Lan
Astle, Clinton M.
Baur, Joseph A.
Sabatini, David M.
Harrison, David E.
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Target of rapamycin inhibition by rapamycin feeding has previously been shown to extend life in genetically heterogeneous mice. To examine whether it similarly affected mouse health, we fed encapsulated rapamycin or a control diet to C57BL/6Nia mice of both sexes starting at 19 months of age. We performed a range of health assessments 6 and 12 months later. Rapamycin feeding significantly reduced mTOR activity in most but not all tissues.

Author(s): 
Zhang, Yiqiang
Bokov, Alex
Gelfond, John
Soto, Vanessa
Ikeno, Yuji
Hubbard, Gene
Diaz, Vivian
Sloane, Lauren
Maslin, Keith
Treaster, Stephen
RÈndon, Samantha
Van Remmen, Holly
Ward, Walter
Javors, Martin
Richardson, Arlan
Austad, Steven N.
Fischer, Kathleen
Publication Title: 
Aging Cell

Rapamycin has been shown to extend lifespan in numerous model organisms including mice, with the most dramatic longevity effects reported in females. However, little is known about the functional ramifications of this longevity-enhancing paradigm in mammalian tissues. We treated 24-month-old female C57BL/6J mice with rapamycin for 3†months and determined health outcomes via a variety of noninvasive measures of cardiovascular, skeletal, and metabolic health for individual mice.

Author(s): 
Flynn, James M.
O'Leary, Monique N.
Zambataro, Christopher A.
Academia, Emmeline C.
Presley, Michael P.
Garrett, Brittany J.
Zykovich, Artem
Mooney, Sean D.
Strong, Randy
Rosen, Clifford J.
Kapahi, Pankaj
Nelson, Michael D.
Kennedy, Brian K.
Melov, Simon
Publication Title: 
Biochemical and Biophysical Research Communications

The development of insulin resistance is the primary step in the etiology of type 2 diabetes mellitus. There are several risk factors associated with insulin resistance, yet the basic biological mechanisms that promote its development are still unclear. There is growing literature that suggests mitochondrial dysfunction and/or oxidative stress play prominent roles in defects in glucose metabolism. Here, we tested whether increased expression of CuZn-superoxide dismutase (Sod1) or Mn-superoxide dismutase (Sod2) prevented obesity-induced changes in oxidative stress and metabolism.

Author(s): 
Liu, Yuhong
Qi, Wenbo
Richardson, Arlan
Van Remmen, Holly
Ikeno, Yuji
Salmon, Adam B.
Publication Title: 
PloS One

Caloric restriction (CR) is argued to positively affect general health, longevity and the normally occurring age-related reduction of cognition. This issue is well examined, but most studies investigated the effect of short-term periods of CR. Herein, 4 weeks old female mice were fed caloric restricted for 4, 20 and especially for 74 weeks. CR mice received 60% of food eaten by their ad libitum (AL) fed littermates, and all age-matched groups were behaviorally analyzed.

Author(s): 
Kuhla, Angela
Lange, Sophie
Holzmann, Carsten
Maass, Fabian
Petersen, Jana
Vollmar, Brigitte
Wree, Andreas
Publication Title: 
Aging Cell

Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown, but has been attributed to extremely rapid aging.

Author(s): 
Brace, Lear E.
Vose, Sarah C.
Vargas, Dorathy F.
Zhao, Shuangyun
Wang, Xiu-Ping
Mitchell, James R.
Publication Title: 
Nature Communications

Metformin is a drug commonly prescribed to treat patients with type 2 diabetes. Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake.

Author(s): 
Martin-Montalvo, Alejandro
Mercken, Evi M.
Mitchell, Sarah J.
Palacios, Hector H.
Mote, Patricia L.
Scheibye-Knudsen, Morten
Gomes, Ana P.
Ward, Theresa M.
Minor, Robin K.
Blouin, Marie-José
Schwab, Matthias
Pollak, Michael
Zhang, Yongqing
Yu, Yinbing
Becker, Kevin G.
Bohr, Vilhelm A.
Ingram, Donald K.
Sinclair, David A.
Wolf, Norman S.
Spindler, Stephen R.
Bernier, Michel
de Cabo, Rafael
Publication Title: 
Nature Communications

Autophagy is a cellular recycling process that has an important anti-aging role, but the underlying molecular mechanism is not well understood. The mammalian transcription factor EB (TFEB) was recently shown to regulate multiple genes in the autophagy process. Here we show that the predicted TFEB orthologue HLH-30 regulates autophagy in Caenorhabditis elegans and, in addition, has a key role in lifespan determination.

Author(s): 
Lapierre, Louis R.
De Magalhaes Filho, C. Daniel
McQuary, Philip R.
Chu, Chu-Chiao
Visvikis, Orane
Chang, Jessica T.
Gelino, Sara
Ong, Binnan
Davis, Andrew E.
Irazoqui, Javier E.
Dillin, Andrew
Hansen, Malene
Publication Title: 
Methods in Molecular Biology (Clifton, N.J.)

Calorie restriction (CR) has a variety of effects on extending lifespan and delaying the onset of age-related diseases, and it is accepted as the only established experimental antiaging intervention. Several pharmacological agents that can replicate the beneficial effects of CR, called calorie restriction mimetics (CRMs), have been identified.

Author(s): 
Kitada, Munehiro
Koya, Daisuke

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