Disease Models, Animal

Publication Title: 
Contributions to Nephrology

Components of the diet related to changes in eating habits that characterize the modern Western world are important factors in the increasingly high prevalence of chronic disease, including obesity, diabetes, hypertension and as a consequence, chronic kidney disease. The healthy diets recommended for the general population to promote longevity (such as the Mediterranean diet), are defined based on epidemiological and intervention studies and are usually characterized by a relatively higher amount of protein than the usual Western diet.

Pecoits-Filho, Roberto
Publication Title: 
The EMBO journal

A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults.

Kim, Dohoon
Nguyen, Minh Dang
Dobbin, Matthew M.
Fischer, Andre
Sananbenesi, Farahnaz
Rodgers, Joseph T.
Delalle, Ivana
Baur, Joseph A.
Sui, Guangchao
Armour, Sean M.
Puigserver, Pere
Sinclair, David A.
Tsai, Li-Huei
Publication Title: 
NestlÈ Nutrition Workshop Series. Paediatric Programme

The focus here is on research involving long-term calorie restriction (CR) to prevent or delay the incidence of the metabolic syndrome with age. The current societal environment is marked by overabundant accessibility of food coupled with a strong trend to reduced physical activity, both leading to the development of a constellation of disorders including central obesity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome). Prolonged CR has been shown to extend median and maximal lifespan in a variety of lower species (yeast, worms, fish, rats, and mice).

Ravussin, Eric
Redman, Leanne M.
Publication Title: 
PloS One

Caloric restriction (CR) extends lifespan through a reduction in oxidative stress, delays the onset of morbidity and prolongs lifespan. We previously reported that long-term CR hastened clinical onset, disease progression and shortened lifespan, while transiently improving motor performance in G93A mice, a model of amyotrophic lateral sclerosis (ALS) that shows increased free radical production.

Patel, Barkha P.
Safdar, Adeel
Raha, Sandeep
Tarnopolsky, Mark A.
Hamadeh, Mazen J.
Publication Title: 
Free Radical Biology & Medicine

Oxidative stress is a prominent feature of Huntington's disease (HD) due to mitochondrial dysfunction and the ensuing overproduction of reactive oxygen species (ROS). This phenomenon ultimately contributes to cognitive and motor impairment, as well as brain pathology, especially in the striatum. Targeting the transcription of the endogenous antioxidant machinery could be a promising therapeutic approach. The NF-E2-related factor-2 (Nrf2)/antioxidant response element (ARE) signaling pathway is an important pathway involved in antioxidant and anti-inflammatory responses.

Stack, Cliona
Ho, Daniel
Wille, Elizabeth
Calingasan, Noel Y.
Williams, Charlotte
Liby, Karen
Sporn, Michael
Dumont, Magali
Beal, M. Flint
Publication Title: 
Neurobiology of Disease

Huntington's disease (HD) is a lethal, neurodegenerative disorder caused by expansion of the polyglutamine repeat in the Huntingtin gene (HTT), leading to mutant protein misfolding, aggregation, and neuronal death. Feeding a Drosophila HD model cystamine, or expressing a transgene encoding the anti-htt intracellular antibody (intrabody) C4-scFv in the nervous system, demonstrated therapeutic potential, but suppression of pathology was incomplete.

Bortvedt, S. F.
McLear, J. A.
Messer, A.
Ahern-Rindell, A. J.
Wolfgang, W. J.
Publication Title: 
Physiology & Behavior

Ketogenic diets are high in fat and low in carbohydrates, and have long been used as an anticonvulsant therapy for drug-intractable and pediatric epilepsy. Additionally, ketogenic diets have been shown to provide neuroprotective effects against acute and chronic brain injury, including beneficial effects in various rodent models of neurodegeneration. Huntington's disease is a progressive neurodegenerative disease characterized by neurological, behavioral and metabolic dysfunction, and ketogenic diets have been shown to increase energy molecules and mitochondrial function.

Ruskin, David N.
Ross, Jessica L.
Kawamura, Masahito
Ruiz, Tiffany L.
Geiger, Jonathan D.
Masino, Susan A.
Publication Title: 
Aging Cell

Nutrient availability influences an organism's life history with profound effects on metabolism and lifespan. The association between a healthy lifespan and metabolism is incompletely understood, but a central factor is glucose metabolism. Although glucose is an important cellular energy source, glucose restriction is associated with extended lifespan in simple animals and a reduced incidence of age-dependent pathologies in humans. We report here that glucose enrichment delays mutant polyglutamine, TDP-43, FUS, and amyloid-?

Tauffenberger, Arnaud
Vaccaro, Alexandra
Aulas, Anais
Vande Velde, Christine
Parker, J. Alex
Publication Title: 
Age (Dordrecht, Netherlands)

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR.

Porquet, David
Casades˙s, Gemma
Bayod, Sergi
Vicente, Alberto
Canudas, Anna M.
Vilaplana, Jordi
PelegrÌ, Carme
Sanfeliu, Coral
Camins, Antoni
Pall‡s, MercË
del Valle, Jaume
Publication Title: 
Trends in endocrinology and metabolism: TEM

The circadian clock machinery orchestrates organism metabolism to ensure that development, survival, and reproduction are attuned to diurnal environmental variations. For unknown reasons, there is a decline in circadian rhythms with age, concomitant with declines in the overall metabolic tissue homeostasis and changes in the feeding behavior of aged organisms.

Tevy, Maria Florencia
Giebultowicz, Jadwiga
Pincus, Zachary
Mazzoccoli, Gianluigi
Vinciguerra, Manlio


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