Transcription, Genetic

Publication Title: 
Mutation Research

During the course of normal respiration, reactive oxygen species are produced which are particularly detrimental to mitochondrial function. This is shown by recent studies with a mouse that lacks the mitochondrial form of superoxide dismutase (Sod2). Tissues that are heavily dependent on mitochondrial function such as the brain and heart are most severely affected in the Sod2 mutant mouse.

Author(s): 
Melov, S.
Coskun, P. E.
Wallace, D. C.
Publication Title: 
Journal of Cell Science

In mammalian cells, products of the INK4a-ARF locus play major roles in senescence and tumour suppression in different contexts, whereas the adjacent INK4b gene is more generally associated with transforming growth factor beta (TGF-beta)-mediated growth arrest. As the chicken genome does not encode an equivalent of INK4a, we asked whether INK4b and/or ARF contribute to replicative senescence in chicken cells.

Author(s): 
Kim, Soo-Hyun
Rowe, Janice
Fujii, Hideta
Jones, Rebecca
Schmierer, Bernhard
Kong, Byung-Whi
Kuchler, Karl
Foster, Douglas
Ish-Horowicz, David
Peters, Gordon
Publication Title: 
Nature

Activating AMPK or inactivating calcineurin slows ageing in Caenorhabditis elegans and both have been implicated as therapeutic targets for age-related pathology in mammals. However, the direct targets that mediate their effects on longevity remain unclear. In mammals, CREB-regulated transcriptional coactivators (CRTCs) are a family of cofactors involved in diverse physiological processes including energy homeostasis, cancer and endoplasmic reticulum stress.

Author(s): 
Mair, William
Morantte, Ianessa
Rodrigues, Ana P. C.
Manning, Gerard
Montminy, Marc
Shaw, Reuben J.
Dillin, Andrew
Publication Title: 
PloS One

Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C.

Author(s): 
Hunt, Piper R.
Son, Tae Gen
Wilson, Mark A.
Yu, Quian-Sheng
Wood, William H.
Zhang, Yongqing
Becker, Kevin G.
Greig, Nigel H.
Mattson, Mark P.
Camandola, Simonetta
Wolkow, Catherine A.
Publication Title: 
Aging Cell

Arsenite is one of the most toxic chemical substances known and is assumed to exert detrimental effects on viability even at lowest concentrations. By contrast and unlike higher concentrations, we here find that exposure to low-dose arsenite promotes growth of cultured mammalian cells. In the nematode C. elegans, low-dose arsenite promotes resistance against thermal and chemical stressors and extends lifespan of this metazoan, whereas higher concentrations reduce longevity. While arsenite causes a transient increase in reactive oxygen species (ROS) levels in C.

Author(s): 
Schmeisser, Sebastian
Schmeisser, Kathrin
Weimer, Sandra
Groth, Marco
Priebe, Steffen
Fazius, Eugen
Kuhlow, Doreen
Pick, Denis
Einax, J¸rgen W.
Guthke, Reinhard
Platzer, Matthias
Zarse, Kim
Ristow, Michael
Publication Title: 
Antioxidants & Redox Signaling

SIGNIFICANCE: Mitochondrial function plays an important role in metabolic homeostasis and has been implicated in aging. Although there is still ongoing debate regarding whether mitochondrion-derived oxidative stress is causative to the aging process, interventions that increase oxidative metabolism and antioxidant pathways in animal models protect against age-related deterioration, such as metabolic diseases and neurodegenerative disorders.

Author(s): 
Liu, Sihao
Reilly, Shannon M.
Lee, Chih-Hao
Publication Title: 
Cell Death and Differentiation

Terminally differentiated neutrophils are short-lived but the key effector cells of the innate immune response, and have a prominent role in the pathogenesis and propagation of many inflammatory diseases. Delayed apoptosis, which is responsible for their extended longevity, is critically dependent on a balance of intracellular survival versus pro-apoptotic proteins. Here, we elucidate the mechanism by which the cyclin-dependent kinase (CDK) inhibitor drugs such as R-roscovitine and DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) mediate neutrophil apoptosis.

Author(s): 
Leitch, A. E.
Lucas, C. D.
Marwick, J. A.
Duffin, R.
Haslett, C.
Rossi, A. G.
Publication Title: 
Aging

The FoxO family of transcription factors plays an important role in longevity and tumor suppression by regulating the expression of a wide range of target genes. FoxO3 has recently been found to be associated with extreme longevity in humans and to regulate the homeostasis of adult stem cell pools in mammals, which may contribute to longevity. The activity of FoxO3 is controlled by a variety of post-translational modifications that have been proposed to form a 'code' affecting FoxO3 subcellular localization, DNA binding ability, protein-protein interactions and protein stability.

Author(s): 
Calnan, Daniel R.
Webb, Ashley E.
White, Jamie L.
Stowe, Timothy R.
Goswami, Tapasree
Shi, Xiaobing
Espejo, Alexsandra
Bedford, Mark T.
Gozani, Or
Gygi, Steven P.
Brunet, Anne
Publication Title: 
Molecular Aspects of Medicine

While the eukaryotic genome is the same throughout all somatic cells in an organism, there are specific structures and functions that discern one type of cell from another. These differences are due to the cell's unique gene expression patterns that are determined during cellular differentiation. Interestingly, these cell-specific gene expression patterns can be affected by an organism's environment throughout its lifetime leading to phenotypical changes that have the potential of altering risk of some diseases.

Author(s): 
Tammen, Stephanie A.
Friso, Simonetta
Choi, Sang-Woon
Publication Title: 
Genesis (New York, N.Y.: 2000)

Aging and reproduction are two defining features of our life. Historically, research has focused on the well-documented decline in reproductive capacity that accompanies old age, especially with increasing maternal age in humans. However, recent experiments in model organisms such as worms, flies, and mice have shown that a dialogue in the opposite direction may be widely prevalent, and that signals from reproductive tissues have a significant effect on the rate of aging of organisms. This pathway has been described in considerable detail in the nematode Caenorhabditis elegans.

Author(s): 
Ghazi, Arjumand

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