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The Buck Institute for Research on Aging is the United States' first independent biomedical research institute devoted solely to research on aging and age-related disease. The mission of the Buck Institute is to extend the healthspan, the healthy years of life.The Institute, a nonprofit organization located in Novato, California, began its research program in 1999. It is named for Marin County philanthropists Leonard and Beryl Hamilton Buck, whose estate funded the generous endowment that helped establish the Institute, and the Buck Trust currently contributes approximately $6 million annually to support the Institute's work. In May 2007, the Institute established a cooperative agreement with the University of California's Davis and Merced campuses to coordinate stem-cell research, a move hailed by UC as a collaboration that "strengthens California's leadership in stem cell research and moves it forward in an efficient, safe and cost-effective manner."The campus of the Buck Institute was designed by architect I. M. Pei, who submitted an unsolicited proposal to design the research facility. Wikipedia.

Brand M.D.,Buck Institute for Age Research
Experimental Gerontology | Year: 2010

Mitochondrial superoxide production is an important source of reactive oxygen species in cells, and may cause or contribute to ageing and the diseases of ageing. Seven major sites of superoxide production in mammalian mitochondria are known and widely accepted. In descending order of maximum capacity they are the ubiquinone-binding sites in complex I (site IQ) and complex III (site IIIQo), glycerol 3-phosphate dehydrogenase, the flavin in complex I (site IF), the electron transferring flavoprotein:Q oxidoreductase (ETFQOR) of fatty acid beta-oxidation, and pyruvate and 2-oxoglutarate dehydrogenases. None of these sites is fully characterized and for some we only have sketchy information. The topology of the sites is important because it determines whether or not a site will produce superoxide in the mitochondrial matrix and be able to damage mitochondrial DNA. All sites produce superoxide in the matrix; site IIIQo and glycerol 3-phosphate dehydrogenase also produce superoxide to the intermembrane space. The relative contribution of each site to mitochondrial reactive oxygen species generation in the absence of electron transport inhibitors is unknown in isolated mitochondria, in cells or in vivo, and may vary considerably with species, tissue, substrate, energy demand and oxygen tension. © 2010 Elsevier Inc.

Campisi J.,Buck Institute for Age Research | Campisi J.,Lawrence Berkeley National Laboratory
Current Opinion in Genetics and Development | Year: 2011

Cellular senescence arrests the proliferation of potential cancer cells, and so is a potent tumor suppressive mechanism, akin to apoptosis. Or is it? Why did cells evolve an anti-cancer mechanism that arrests, rather than kills, would-be tumor cells? Recent discoveries that senescent cells secrete growth factors, proteases and cytokines provide a shifting view-from senescence as a cell autonomous suppressor of tumorigenesis to senescence as a means to mobilize the systemic and local tissue milieu for repair. In some instances, this mobilization benefits the organism, but in others it can be detrimental. These discoveries provide potential mechanisms by which cellular senescence might contribute to the diverse, and seemingly incongruent, processes of tumor suppression, tumor promotion, tissue repair, and aging. © 2010 Elsevier Ltd.

Burtner C.R.,University of Washington | Kennedy B.K.,University of Washington | Kennedy B.K.,Buck Institute for Age Research | Kennedy B.K.,Guangdong Medical College
Nature Reviews Molecular Cell Biology | Year: 2010

One of the many debated topics in ageing research is whether progeroid syndromes are really accelerated forms of human ageing. The answer requires a better understanding of the normal ageing process and the molecular pathology underlying these rare diseases. Exciting recent findings regarding a severe human progeria, Hutchinsonĝ€"Gilford progeria syndrome, have implicated molecular changes that are also linked to normal ageing, such as genome instability, telomere attrition, premature senescence and defective stem cell homeostasis in disease development. These observations, coupled with genetic studies of longevity, lead to a hypothesis whereby progeria syndromes accelerate a subset of the pathological changes that together drive the normal ageing process. © 2010 Macmillan Publishers Limited. All rights reserved.

Azzu V.,MRC Mitochondrial Biology Unit | Brand M.D.,MRC Mitochondrial Biology Unit | Brand M.D.,Buck Institute for Age Research
Trends in Biochemical Sciences | Year: 2010

Mitochondrial uncoupling proteins disengage substrate oxidation from ADP phosphorylation by dissipating the proton electrochemical gradient that is required for ATP synthesis. In doing this, the archetypal uncoupling protein, UCP1, mediates adaptive thermogenesis. By contrast, its paralogues UCP2 and UCP3 are not thought to mediate whole body thermogenesis in mammals. Instead, they have been implicated in a variety of physiological and pathological processes, including protection from oxidative stress, negative regulation of glucose sensing systems and the adaptation of fatty acid oxidation capacity to starving. Although much work has been devoted to how these proteins are activated, little is known of the mechanisms that reverse this activation. © 2009 Elsevier Ltd.

Kapahi P.,Buck Institute for Age Research
Advances in Experimental Medicine and Biology | Year: 2010

Growth and somatic maintenance are thought to be antagonistic pleiotropic 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. Furthermore, dietary restriction (DR) that leads to antagonistic changes in growth and lifespan, also mediates this change by inhibiting protein synthesis. Direct screens to identify genes that extend lifespan from a subset of genes that are essential for growth and development have also uncovered a number of genes involved in protein synthesis. Given the conservedmechanisms of protein synthesis across species, I discuss potential mechanisms that mediate the lifespan extension by inhibition of protein synthesis that are likely to be important for aging and age-related disorders in humans. ©2010 Landes Bioscience and Springer Science+Business Media.

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