Using Poisson-gamma model to evaluate the duration of recruitment process when historical trials are available.

At the design of clinical trial operation, a question of a paramount interest is how long it takes to recruit a given number of patients. Modelling the recruitment dynamics is the necessary step to answer this question. Poisson-gamma model provides very convenient, flexible and realistic approach.

How to deal with the Poisson-gamma model to forecast patients' recruitment in clinical trials when there are pauses in recruitment dynamic?

Recruiting patients is a crucial step of a clinical trial. Estimation of the trial duration is a question of paramount interest. Most techniques are based on deterministic models and various methods neglecting the variability in the recruitment process.

Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan.

Several pathways modulating longevity and stress resistance converge on translation by targeting ribosomal proteins or initiation factors, but whether this involves modifications of ribosomal RNA is unclear. Here, we show that reduced levels of the conserved RNA methyltransferase NSUN5 increase the lifespan and stress resistance in yeast, worms and flies. Rcm1, the yeast homologue of NSUN5, methylates C2278 within a conserved region of 25S rRNA.

Phosphatidylethanolamine positively regulates autophagy and longevity.

Autophagy is a cellular recycling program that retards ageing by efficiently eliminating damaged and potentially harmful organelles and intracellular protein aggregates. Here, we show that the abundance of phosphatidylethanolamine (PE) positively regulates autophagy. Reduction of intracellular PE levels by knocking out either of the two yeast phosphatidylserine decarboxylases (PSD) accelerated chronological ageing-associated production of reactive oxygen species and death.

Spermidine feeding decreases age-related locomotor activity loss and induces changes in lipid composition.

Spermidine is a natural polyamine involved in many important cellular functions, whose supplementation in food or water increases life span and stress resistance in several model organisms. In this work, we expand spermidine's range of age-related beneficial effects by demonstrating that it is also able to improve locomotor performance in aged flies. Spermidine's mechanism of action on aging has been primarily related to general protein hypoacetylation that subsequently induces autophagy.

Molecular basis of the 'anti-aging' effect of spermidine and other natural polyamines - a mini-review.

Background: Spermidine, a naturally occurring polyamine, has recently emerged as exhibiting anti-aging properties. Its supplementation increases lifespan and resistance to stress, and decreases the occurrence of age-related pathology and loss of locomotor ability. Its mechanisms of action are just beginning to be understood.

Spermidine promotes stress resistance in Drosophila melanogaster through autophagy-dependent and -independent pathways.

The naturally occurring polyamine spermidine (Spd) has recently been shown to promote longevity across species in an autophagy-dependent manner. Here, we demonstrate that Spd improves both survival and locomotor activity of the fruit fly Drosophila melanogaster upon exposure to the superoxide generator and neurotoxic agent paraquat. Although survival to a high paraquat concentration (20 mM) was specifically increased in female flies only, locomotor activity and survival could be rescued in both male and female animals when exposed to lower paraquat levels (5 mM).

Polyamines in aging and disease.

Polyamines are polycations that interact with negatively charged molecules such as DNA, RNA and proteins. They play multiple roles in cell growth, survival and proliferation. Changes in polyamine levels have been associated with aging and diseases.

RNA interference in ageing research--a mini-review.

Background: The search for genetic mechanisms affecting life-span and ageing represents an important part of ageing research, especially since the discovery of single-gene mutations with dramatic effects on these traits. Due to its relative ease of use and its power to specifically target arbitrary genes, RNA interference (RNAi) has rapidly been adopted as a technique for silencing gene expression. The feasibility of genome-wide RNAi screens potentially much simplifies the identification of novel ageing-related genes.

Induction of autophagy by spermidine promotes longevity.

Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice.

Plasticity of death rates in stationary phase in Saccharomyces cerevisiae.

For the species that have been most carefully studied, mortality rises with age and then plateaus or declines at advanced ages, except for yeast. Remarkably, mortality for yeast can rise, fall and rise again. In the present study we investigated (i) if this complicated shape could be modulated by environmental conditions by measuring mortality with different food media and temperature; (ii) if it is triggered by biological heterogeneity by measuring mortality in stationary phase in populations fractionated into subpopulations of young, virgin cells, and replicatively older, non-virgin cells.

The hormetic effects of hypergravity on longevity and aging.

This paper reviews the literature on the effects of hypergravity (HG, gravity levels higher than 1g, the terrestrial gravity) on longevity and aging. The different studies showed that life-long exposures to high gravity levels decreased longevity and accelerated the age-related decline observed on some physiological and behavioral variables. In contrast, chronic exposure to HG increased resistance to heat in young and middle-aged Drosophila melanogaster.

The use of genetically engineered model systems for research on human aging.

A major goal in the field of aging research is to identify molecular mechanisms of aging at the cellular level, which are anticipated to form the basis for the development of age-associated dysfunctions and diseases in human beings. Recent progress in research into model organisms of aging has allowed determining precise molecular mechanisms and genetic determinants of the aging process, which appear to be conserved in evolution and some of which apply to human aging as well. The consortium of the authors focuses on aging mechanisms at the cellular level, and exploits the potential of genetic analyses in lower eukaryotic model organisms for a better understanding of regulatory pathways implicated in aging processes.

Symmetrically dividing cells of the fission yeast schizosaccharomyces pombe do age.

Theories of the evolution of senescence state that symmetrically dividing organisms do not senesce. However, this view is challenged by experimental evidence. We measured by immunofluorescence the occurrence and intensity of protein carbonylation in single and symmetrically dividing cells of Schizosaccharomyces pombe.

How should we assess the impact of genetic changes on ageing in model species?

One of the most active branches of genetic research is the quest for the genetic determinants of ageing. The ultimate goal of much of this effort is to understand ageing in humans. In addition to work on human genetics, many researchers look to model organisms in order to find genetic variation that can affect ageing.

Does dietary restriction really increase longevity in Drosophila melanogaster?

It is often accepted that dietary restriction (DR) increases longevity in most species so far tested. Showing the same result in the fruit fly Drosophila melanogaster would be of interest, because this species is widely used in aging research. Some studies have shown that dietary restriction decreases longevity in this species while the opposite result has also been reported.

Advances in measuring lifespan in the yeast Saccharomyces cerevisiae.

Much research aimed at discovering the genetic bases of longevity focuses on the budding yeast Saccharomyces cerevisiae. Unfortunately, yeast researchers use a definition of longevity not applied to other species. We propose here a method that makes it possible to estimate for yeast the same measures of longevity calculated for other species.

Chronological aging-independent replicative life span regulation by Msn2/Msn4 and Sod2 in Saccharomyces cerevisiae.

Mutations in RAS2, CYR1, and SCH9 extend the chronological life span in Saccharomyces cerevisiae by activating stress-resistance transcription factors and mitochondrial superoxide dismutase (Sod2). Here we show that mutations in CYR1 and SCH9 also extend the replicative life span of individual yeast mother cells. However, the triple deletion of stress-resistance genes MSN2/MSN4 and RIM15, which causes a major decrease in chronological life span, extends replicative life span.

Biodemographic trajectories of age-specific reproliferation from stationary phase in the yeast Saccharomyces cerevisiae seem multiphasic.

Ageing is usually seen as a monotonic decline of functions and survival. However, recent studies reported that age-specific mortality rates increased and then leveled off or even declined at later ages in several species including humans. Preliminary data using the yeast, Saccharomyces cerevisiae, demonstrated an even more complicated, non-monotonic pattern of reproliferation after stationary phase (i.

Fecundity and life span in transgenic Drosophila melanogaster overexpressing hsp70.

In the present study, we investigated the effect of hsp70 overexpression on some life history components in transgenic fruit flies. We measured life span in mated flies and fecundity in flies subjected or not subjected to a heat shock inducing hsp70. Heat shock increased life span of the parental line, but not of the transgenic lines.

A mild stress due to hypergravity exposure at young age increases longevity in Drosophila melanogaster males.

Drosophila melanogaster flies were exposed to hypergravity starting at two days of age, the range of gravity levels used being 2.58-7.38 g.

Longevity and aging: beneficial effects of exposure to mild stress.

Every organism has to deal with exposure to stresses. Animals have developed various strategies to cope with stress. It appears that the developed resistance to stress is often related to longevity.

Resistance to stress as a function of age in transgenic Drosophila melanogaster overexpressing Hsp70.

This study investigated the resistance to stress as a function of age in Drosophila melanogaster overexpressing Hsp70. The resistances to starvation, paraquat, and cold in flies from 1 to 7 week-old have been measured. The line carrying the insertion vector without the transgenes is more resistant to starvation and cold than the parental and transgenic lines.