T B L Kirkwood

..AVAILABILITY: All tools described are available from http://www.basis.ncl.ac.uk/software and are licensed under GNU General Public License...

..g. food supply. Evolutionary understanding can also help to understand important features of the human life history such as menopause...

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..The 'Fluorimetric Detection of Alkaline DNA Unwinding (FADU)' method [Birnboim HC, Jevcak JJ. Cancer Res (1981) 41:1889-1892] is a sensitive procedure to quantify DNA strand breaks, yet it is very tedious to perform...

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..It will then be important to investigate how these are organised and whether the same or different factors are at play in the various species in which food restriction extends life span...

..An elegant new study of genes acting downstream of these signals in the nematode worm Caenorhabditis elegans reveals a plethora of information about the complex network of mechanisms that modulate the ageing process...

..To understand the cell and molecular basis of aging is to unravel the multiplicity of mechanisms causing damage to accumulate and the complex array of systems working to keep damage at bay...

..In this article we review what is currently understood about the factors underlying the variability of life span and consider the implications for research that aims to improve the predictability of health in old age...

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..This connection is informed by actions of natural selection on the determinants of ageing and longevity...

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..Growing evidence indicates that the global aging process is more malleable than used to be thought. This needs to be taken into account in efforts to improve health and retention of mental capital across the life course...

..This is most striking in the case of the human menopause, for which a particular combination of biological and sociobiological factors appear to be responsible...

..In acknowledging that, at least in theory, ageing might occasionally be adaptive, however, the high barriers to validating actual instances of adaptive ageing are made clear...

..This paper reviews what is currently known about intrinsic ageing of gut epithelial stem cells and its functional consequences...

..Recognition that ageing results from accumulation of damage also points to a role for lifestyle interventions (e.g. nutrition and exercise) to help prevent damage or promote repair...

..An ambitious strategy for future research on ageing and age-related disorders is based on the synergy between these complementary approaches...

..The model can be used to carry out a variety of in silico experiments in which different genes are knocked out and the results of simulation are compared to experimental data. Possible extensions to the model are also discussed...

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..Our results point to the distinctive (and perhaps unique) role of menopause in human evolution and provide important support for the hypothesized evolutionary significance of grandmothers...

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..Although calorie restriction does not increase lifespan in all species, it remains a fascinating and valuable tool to study ageing at the whole organism level...

..We suggest that theoretical models of this kind are valuable tools to bridge the gap between the verbal statements of hypotheses and their rigorous experimental test...

..By letting the probability of uncapping depend upon telomere length, we show that the hypothesized model provides a good fit to experimental data...

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..We describe how a new web-based modelling initiative is seeking to integrate data and hypotheses from diverse biological sources...

..We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated...

..X foci. We propose that mitochondrial ROS is a major determinant of telomere-dependent senescence at the single-cell level that is responsible for cell-to-cell variation in replicative lifespan...

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..But other work shows that there is a strong positive association between DNA repair-mediated protection against cancer and ageing. So what are we to make of the new data with regard to overall understanding of the mechanisms of ageing?..

..Our results thus establish that PARP-1 acts as a survival factor for intestinal stem cells in vivo and suggest a functional link with early p53 and p21(CIP1/WAF1) responses...

..We show for the first time in aging human tissue that RC deficiency attenuates cell proliferation and increases apoptosis in the progeny of RC deficient stem cells, leading to decreased crypt cell population...

..These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell...

..The unusual antioxidant status of beta-cells may thus be explained as an instance of co-evolution of the brain, cortisol and corticosteroid receptors, and beta-cells in the endocrine pancreas...

..We also describe how the optimal investment in maintenance is affected by varying the parameters that specify the schedules of reproduction and mortality...

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..Our results therefore suggest that in terms of maintenance of the cellular immune system, senescence of the honeybee worker is under social control...