Oligonucleotide Array Sequence Analysis

Publication Title: 
Mechanisms of Ageing and Development

It is widely held that caloric restriction (CR) extends lifespan by preventing or reducing the age-related accumulation of irreversible molecular damage. In contrast, our results suggest that CR can act rapidly to begin life and health span extension, and that its rapid genomic effects are closely linked to its health effects. We found that CR begins to extend lifespan and reduce cancer as a cause of death within 8 weeks in older mice, apparently by reducing the rate of tumor growth.

Author(s): 
Spindler, Stephen R.
Publication Title: 
Toxicology and Applied Pharmacology

The ID (inhibitor of differentiation or DNA binding) helix-loop-helix proteins are important mediators of cellular differentiation and proliferation in a variety of cell types through regulation of gene expression. Overexpression of the ID proteins in normal human keratinocytes results in extension of culture lifespan, indicating that these proteins are important for epidermal differentiation. Our hypothesis is that the ID proteins are targets of the retinoic acid signaling pathway in keratinocytes.

Author(s): 
Villano, C. M.
White, L. A.
Publication Title: 
Gerontology

BACKGROUND: We review studies showing that CR acts rapidly, even in late adulthood, to extend health- and lifespan in mice. These rapid physiological effects are closely linked to patterns of gene expression in liver and heart. Non-human primate and human studies suggest that the signal transduction pathways responsible for the lifespan and health effects of caloric restriction (CR) may also be involved in human longevity. Thus, pharmaceuticals capable of mimicking the effects of CR (and other methods of lifespan extension) may have application to human health.

Author(s): 
Spindler, Stephen R.
Mote, Patricia L.
Publication Title: 
PLoS genetics

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan. Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice.

Author(s): 
Schumacher, Bjˆrn
van der Pluijm, Ingrid
Moorhouse, Michael J.
Kosteas, Theodore
Robinson, Andria Rasile
Suh, Yousin
Breit, Timo M.
van Steeg, Harry
Niedernhofer, Laura J.
van Ijcken, Wilfred
Bartke, Andrzej
Spindler, Stephen R.
Hoeijmakers, Jan H. J.
van der Horst, Gijsbertus T. J.
Garinis, George A.
Publication Title: 
BMC bioinformatics

BACKGROUND: Differential coexpression is a change in coexpression between genes that may reflect 'rewiring' of transcriptional networks. It has previously been hypothesized that such changes might be occurring over time in the lifespan of an organism. While both coexpression and differential expression of genes have been previously studied in life stage change or aging, differential coexpression has not. Generalizing differential coexpression analysis to many time points presents a methodological challenge.

Author(s): 
Gillis, Jesse
Pavlidis, Paul
Publication Title: 
Geriatrics & Gerontology International

Lifespan can be lengthened by genetic and environmental modifications. Study of these might provide valuable insights into the mechanism of aging. Low doses of radiation and short-term exposure to heat and high concentrations of oxygen prolong the lifespan of the nematode Caenorhabditis elegans. These might be caused by adaptive responses to harmful environmental conditions. Single-gene mutations have been found to extend lifespan in C. elegans, Drosophila and mice. So far, the best-characterized system is the C.

Author(s): 
Honda, Yoko
Tanaka, Masashi
Honda, Shuji
Publication Title: 
Annals of the New York Academy of Sciences

By applying calorie restriction (CR) at 30-50% below ad libitum levels, studies in numerous species have reported increased life span, reduced incidence and delayed onset of age-related diseases, improved stress resistance, and decelerated functional decline. Whether this nutritional intervention is relevant to human aging remains to be determined; however, evidence emerging from CR studies in nonhuman primates suggests that response to CR in primates parallels that observed in rodents. To evaluate CR effects in humans, clinical trials have been initiated.

Author(s): 
Ingram, Donald K.
Anson, R. Michael
de Cabo, Rafael
Mamczarz, Jacek
Zhu, Min
Mattison, Julie
Lane, Mark A.
Roth, George S.
Publication Title: 
Mechanisms of Ageing and Development

It is widely held that caloric restriction (CR) extends lifespan by preventing or reducing the age-related accumulation of irreversible molecular damage. In contrast, our results suggest that CR can act rapidly to begin life and health span extension, and that its rapid genomic effects are closely linked to its health effects. We found that CR begins to extend lifespan and reduce cancer as a cause of death within 8 weeks in older mice, apparently by reducing the rate of tumor growth.

Author(s): 
Spindler, Stephen R.
Publication Title: 
NestlÈ Nutrition Workshop Series. Clinical & Performance Programme
Author(s): 
Weindruch, Richard
Kayo, Tsuyoshi
Lee, Cheol-Koo
Prolla, Tomas A.
Publication Title: 
Annual Review of Nutrition

Caloric restriction (CR), the consumption of fewer calories without malnutrition, and reduced insulin and/or IGFI receptor signaling delay many age-related physiological changes and extend the lifespan of many model organisms. Here, we present and review microarray and biochemical studies indicating that the potent anticancer effects of CR and disrupted insulin/IGFI receptor signaling evolved as a byproduct of the role of many mitotic tissues as reservoirs of metabolic energy.

Author(s): 
Spindler, Stephen R.
Dhahbi, Joseph M.

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