Intracellular Signaling Peptides and Proteins

Publication Title: 
Investigative Ophthalmology & Visual Science

PURPOSE: To investigate the migratory and contractile behavior of isolated human corneal fibroblasts in fibrillar collagen matrices. METHODS: A telomerase-infected, extended-lifespan human corneal fibroblast cell line (HTK) was transfected by using a vector for enhanced green fluorescent protein (GFP)-alpha-actinin. Cells were plated at low density on top of or within 100-microm-thick fibrillar collagen lattices. After 18 hours to 7 days, time-lapse imaging was performed.

Author(s): 
Vishwanath, Mridula
Ma, Lisha
Otey, Carol A.
Jester, James V.
Petroll, W. Matthew
Publication Title: 
Rejuvenation Research

Can we extend human lifespan? Do we need to regulate lifestyle choices or can we simply pop a pill to make us live longer? These are questions raised by two new studies demonstrating significant lifespan extension in mice fed the drug rapamycin in their diet and in calorically restricted rhesus monkeys.

Author(s): 
Cox, Lynne S.
Publication Title: 
Current Opinion in Drug Discovery & Development

TOR (target of rapamycin) is a serine-threonine protein kinase that is conserved across a diverse range of species from fungi to mammals. The signaling pathway that is anchored by TOR is also conserved across species. In mammals, mTOR integrates growth factor, amino acid, nutrient and energy sensing signals, and thus plays a major role in cell growth and proliferation, protein synthesis and autophagy.

Author(s): 
Sudarsanam, Sucha
Johnson, Dale E.
Publication Title: 
Aging Cell

Dietary restriction (DR) is a robust nongenetic, nonpharmacological intervention that is known to increase active and healthy lifespan in a variety of species. Despite a variety of differences in the protocols and the way DR is carried out in different species, conserved relationships are emerging among multiple species. 2009 saw the field of DR mature with important mechanistic insights from multiple species. A report of lifespan extension in rapamycin-treated mice suggested that the TOR pathway, a conserved mediator of DR in invertebrates, may also be critical to DR effects in mammals.

Author(s): 
Katewa, Subhash D.
Kapahi, Pankaj
Publication Title: 
Cell Cycle (Georgetown, Tex.)

Although it has been known since 1917 that calorie restriction (CR) decelerates aging, the topic remains highly controversial. What might be the reason? Here I discuss that the anti-aging effect of CR rules out accumulation of DNA damage and failure of maintenance as a cause of aging. Instead, it suggests that aging is driven in part by the nutrient-sensing TOR (target of rapamycin) network. CR deactivates the TOR pathway, thus slowing aging and delaying diseases of aging.

Author(s): 
Blagosklonny, Mikhail V.
Publication Title: 
Advances in Experimental Medicine and Biology

Growth and somatic maintenance are thought to be antagonistic piciotropic traits, but the molecular basis for this tradeoff is poorly understood. Here it is proposed that changes in protein synthesis mediate the tradeoffs that take place upon genetic and environmental manipulation in various model systems including yeast, worms, flies and mice. This hypothesis is supported by evidence that inhibition of the TOR (target of rapamycin) pathway and various translation factors that inhibit protein synthesis lead to slowing of growth and development but extend lifespan.

Author(s): 
Kapahi, Pankaj
Publication Title: 
Genes & Development

Alterations in the architecture and dynamics of the nuclear lamina have a causal role in normal and accelerated aging through both cell-autonomous and systemic mechanisms. However, the precise nature of the molecular cues involved in this process remains incompletely defined. Here we report that the accumulation of prelamin A isoforms at the nuclear lamina triggers an ATM- and NEMO-dependent signaling pathway that leads to NF-?B activation and secretion of high levels of proinflammatory cytokines in two different mouse models of accelerated aging (Zmpste24(-/-) and Lmna(G609G/G609G) mice).

Author(s): 
Osorio, Fernando G.
B·rcena, Clea
Soria-Valles, Clara
Ramsay, Andrew J.
de Carlos, FÈlix
Cobo, Juan
Fueyo, Antonio
Freije, JosÈ M. P.
LÛpez-OtÌn, Carlos
Publication Title: 
Molecular and Cellular Biology

The DNA damage response (DDR) is critical for genome stability and the suppression of a wide variety of human malignancies, including neurodevelopmental disorders, immunodeficiency, and cancer. In addition, the efficacy of many chemotherapeutic strategies is dictated by the status of the DDR. Ubiquitin-specific protease 28 (USP28) was reported to govern the stability of multiple factors that are critical for diverse aspects of the DDR. Here, we examined the effects of USP28 depletion on the DDR in cells and in vivo.

Author(s): 
Knobel, Philip A.
Belotserkovskaya, Rimma
Galanty, Yaron
Schmidt, Christine K.
Jackson, Stephen P.
Stracker, Travis H.
Publication Title: 
Rejuvenation Research

Can we extend human lifespan? Do we need to regulate lifestyle choices or can we simply pop a pill to make us live longer? These are questions raised by two new studies demonstrating significant lifespan extension in mice fed the drug rapamycin in their diet and in calorically restricted rhesus monkeys.

Author(s): 
Cox, Lynne S.
Publication Title: 
Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan

Senescence Marker Protein-30 (SMP30) was originally identified as a novel protein in the rat liver, the expression of which decreases with aging. Recently, we identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonases (GNL) of animal species. GNL was a key enzyme which involved in vitamin C biosynthesis, and the essential role of SMP30 in this synthetic process was verified by a nutritional study. SMP30 knockout mice developed symptoms of scurvy when fed a vitamin C-deficient diet, verifying the pivotal role of SMP30 in vitamin C biosynthesis.

Author(s): 
Ishigami, Akihito

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