Heat-Shock Response

Publication Title: 
Biochemical and Biophysical Research Communications

Clusterin is a disulfide-linked heterodimeric glycoprotein that has been implicated in a variety of biological processes. Its expression has been shown to be elevated during cellular senescence and normal aging, but it is uncertain whether clusterin protects against aging or whether its expression is a consequence of aging. To investigate the functions of clusterin during organismal aging, we established transgenic Drosophila alleles to induce the expression of the secretory form of human clusterin (hClu(S)) using the Gal4/UAS system.

Lee, Young-Nam
Shim, Young-Jun
Kang, Byeong-Ho
Park, Joong-Jean
Min, Bon-Hong
Publication Title: 
Medical Hypotheses

Naturally occurring T regulatory cells targeting epitopes derived from various heat shock proteins escape thymic negative selection and can be activated by vaccination with heat shock proteins; hence, vaccination with such proteins has exerted favorable effects on rodent models of autoimmune disorders.

McCarty, Mark F.
Al-Harbi, Saleh A.
Publication Title: 
Molecular Microbiology

Barring genetic manipulation, the diet known as calorie restriction (CR) is currently the only way to slow down ageing in mammals. The fact that CR works on most species, even microorganisms, implies a conserved underlying mechanism. Recent findings in the yeast Saccharomyces cerevisiae indicate that CR extends lifespan because it is a mild biological stressor that activates Sir2, a key component of yeast longevity and the founding member of the sirtuin family of deacetylases.

Lamming, Dudley W.
Wood, Jason G.
Sinclair, David A.
Publication Title: 
The Journal of Biological Chemistry

The life span of model organisms can be modulated by environmental conditions that influence cellular metabolism, oxidation, or DNA integrity. The yeast nicotinamidase gene pnc1 was identified as a key transcriptional target and mediator of calorie restriction and stress-induced life span extension. PNC1 is thought to exert its effect on yeast life span by modulating cellular nicotinamide and NAD levels, resulting in increased activity of Sir2 family class III histone deacetylases.

Balan, Vitaly
Miller, Gregory S.
Kaplun, Ludmila
Balan, Karina
Chong, Zhao-Zhong
Li, Faqi
Kaplun, Alexander
VanBerkum, Mark F. A.
Arking, Robert
Freeman, D. Carl
Maiese, Kenneth
Tzivion, Guri
Publication Title: 
Science (New York, N.Y.)
Saunders, Laura R.
Verdin, Eric
Publication Title: 
Neurobiology of Aging

Heat shock response, mediated by heat shock proteins, is a highly conserved physiological process in multicellular organisms for reestablishment of cellular homeostasis. Expression of heat shock factors and subsequent heat shock protein plays a role in protection against proteotoxicity in invertebrate and vertebrate models. Proteotoxicity due to beta-amyloid peptide (Abeta) oligomerization has been linked to the pathogenesis of Alzheimer's disease.

Wu, Yanjue
Cao, Zhiming
Klein, William L.
Luo, Yuan
Publication Title: 

Rosa damascena, or Damask rose, is a rose hybrid commonly harvested for rose oil used in perfumery and for rose water used to flavor food. The petal extract of R. damascena was recently found to decrease Drosophila melanogaster mortality without impairing reproductive fitness or metabolic rate. Here, we report that R. damascena extended both mean and maximum lifespan of the fly. The extract also protected against oxidative stress in flies, predominantly in females.

Schriner, Samuel E.
Katoozi, Niki S.
Pham, Kevin Q.
Gazarian, Maral
Zarban, Asghar
Jafari, Mahtab
Publication Title: 
FASEB journal: official publication of the Federation of American Societies for Experimental Biology

Adult-onset, long-term caloric restriction (CR) prolongs maximum life span in laboratory rodents. However, the effect of this intervention on an organism's ability to cope with a physical challenge has not been explored. We investigated the influence of CR and aging on stress tolerance in old rats exposed to an environmental heating protocol on two consecutive days. We hypothesized that CR would increase heat tolerance by reducing cellular stress and subsequent accrual of oxidative injury.

Hall, D. M.
Oberley, T. D.
Moseley, P. M.
Buettner, G. R.
Oberley, L. W.
Weindruch, R.
Kregel, K. C.
Publication Title: 

Mammalian models of longevity are related primarily to caloric restriction and alterations in metabolism. We examined mice in which type 5 adenylyl cyclase (AC5) is knocked out (AC5 KO) and which are resistant to cardiac stress and have increased median lifespan of approximately 30%. AC5 KO mice are protected from reduced bone density and susceptibility to fractures of aging. Old AC5 KO mice are also protected from aging-induced cardiomyopathy, e.g., hypertrophy, apoptosis, fibrosis, and reduced cardiac function.

Yan, Lin
Vatner, Dorothy E.
O'Connor, J. Patrick
Ivessa, Andreas
Ge, Hui
Chen, Wei
Hirotani, Shinichi
Ishikawa, Yoshihiro
Sadoshima, Junichi
Vatner, Stephen F.
Publication Title: 
The Journal of Biological Chemistry

The heat shock response (HSR) is responsible for maintaining cellular and organismal health through the regulation of proteostasis. Recent data demonstrating that the mammalian HSR is regulated by SIRT1 suggest that this response may be under metabolic control. To test this hypothesis, we have determined the effect of caloric restriction in Caenorhabditis elegans on activation of the HSR and have found a synergistic effect on the induction of hsp70 gene expression. The homolog of mammalian SIRT1 in C. elegans is Sir2.1. Using a mutated C.

Raynes, Rachel
Leckey, Bruce D.
Nguyen, Kevin
Westerheide, Sandy D.


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