Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

The maintenance gap: a new theoretical perspective on the evolution of aging

One of the prevailing theories of aging, the disposable soma theory, views aging as the result of the accumulation of damage through imperfect maintenance. Aging, then, is explained from an evolutionary perspective by asserting that this lack of maintenance exists because the required resources are better invested in reproduction. However, the amount of maintenance necessary to prevent aging, ‘maintenance requirement’ has so far been largely neglected and has certainly not been considered from an evolutionary perspective. To our knowledge we are the first to do so, and arrive at the conclusion that all maintenance requirement needs an evolutionary explanation. Increases in maintenance requirement can only be selected for if these are linked with either higher fecundity or better capabilities to cope with environmental challenges to the integrity of the organism. Several observations are suggestive of the latter kind of trade-off, the existence of which leads to the inevitable conclusion that the level of maintenance requirement is in principle unbound. Even the allocation of all available resources to maintenance could be unable to stop aging in some organisms. This has major implications for our understanding of the aging process on both the evolutionary and the mechanistic level. It means that the expected effect of measures to reallocate resources to maintenance from reproduction may be small in some species. We need to have an idea of how much maintenance is necessary in the first place. Our explorations of how natural selection is expected to act on the maintenance requirement provides the first step in understanding this

Mitochondrial phylogeography of baboons (Papio spp.) – Indication for introgressive hybridization?

<p>Abstract</p> <p>Background</p> <p>Baboons of the genus <it>Papio </it>are distributed over wide ranges of Africa and even colonized parts of the Arabian Peninsula. Traditionally, five phenotypically distinct species are recognized, but recent molecular studies were not able to resolve their phylogenetic relationships. Moreover, these studies revealed para- and polyphyletic (hereafter paraphyletic) mitochondrial clades for baboons from eastern Africa, and it was hypothesized that introgressive hybridization might have contributed substantially to their evolutionary history. To further elucidate the phylogenetic relationships among baboons, we extended earlier studies by analysing the complete mitochondrial cytochrome <it>b </it>gene and the 'Brown region' from 67 specimens collected at 53 sites, which represent all species and which cover most of the baboons' range.</p> <p>Results</p> <p>Based on phylogenetic tree reconstructions seven well supported major haplogroups were detected, which reflect geographic populations and discordance between mitochondrial phylogeny and baboon morphology. Our divergence age estimates indicate an initial separation into southern and northern baboon clades 2.09 (1.54–2.71) million years ago (mya). We found deep divergences between haplogroups within several species (~2 mya, northern and southern yellow baboons, western and eastern olive baboons and northern and southern chacma baboons), but also recent divergence ages among species (< 0.7 mya, yellow, olive and hamadryas baboons in eastern Africa).</p> <p>Conclusion</p> <p>Our study confirms earlier findings for eastern Africa, but shows that baboon species from other parts of the continent are also mitochondrially paraphyletic. The phylogenetic patterns suggest a complex evolutionary history with multiple phases of isolation and reconnection of populations. Most likely all these biogeographic events were triggered by multiple cycles of expansion and retreat of savannah biomes during Pleistocene glacial and inter-glacial periods. During contact phases of populations reticulate events (i.e. introgressive hybridization) were highly likely, similar to ongoing hybridization, which is observed between East African baboon populations. Defining the extent of the introgressive hybridization will require further molecular studies that incorporate additional sampling sites and nuclear loci.</p

Four Novel Loci (19q13, 6q24, 12q24, and 5q14) Influence the Microcirculation In Vivo

Jaakko Tuomilehto Global BPgen Consortium'n jäsenPeer reviewe

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries