118 research outputs found
The Size-Life Span Trade-Off Decomposed: Why Large Dogs Die Young
No full textLarge body size is one of the best predictors of long life span across species of mammals. In marked contrast, there is considerable evidence that, within species, larger individuals are actually shorter lived. This apparent cost of larger size is especially evident in the domestic dog, where artificial selection has led to breeds that vary in body size by almost two orders of magnitude and in average life expectancy by a factor of two. Survival costs of large size might be paid at different stages of the life cycle: a higher early mortality, an early onset of senescence, an elevated baseline mortality, or an increased rate of aging. After fitting different mortality hazard models to death data from 74 breeds of dogs, we describe the relationship between size and several mortality components. We did not find a clear correlation between body size and the onset of senescence. The baseline hazard is slightly higher in large dogs, but the driving force behind the trade-off between size and life span is apparently a strong positive relationship between size and aging rate. We conclude that large dogs die young mainly because they age quickly.American Federation of Aging Researc
Protein networks, pleiotropy and the evolution of senescence
No full textThe number of interactions, or connectivity, among proteins in the yeast protein interaction network follows a power law. I compare patterns of connectivity for subsets of yeast proteins associated with senescence and with five other traits. I find that proteins associated with ageing have significantly higher connectivity than expected by chance, a pattern not seen for most other datasets. The pattern holds even when controlling for other factors also associated with connectivity, such as localization of protein expression within the cell. I suggest that these observations are consistent with the antagonistic pleiotropy theory for the evolution of senescence. In further support of this argument, I find that a protein’s con-nectivity is positively correlated with the number of traits it influences or its degree of pleiotropy, and further show that the average degree of pleiotropy is greatest for proteins associated with senescence. I explain these results with a simple mathematical model combining assumptions of the antagonistic pleio-tropy theory for the evolution of senescence with data on network topology. These findings integrate molecular and evolutionary models of senescence, and should aid in the search for new ageing genes
NEW PERSPECTIVES ON COMPARATIVE TESTS OF ANTAGONISTIC PLEIOTROPY USING <i>DROSOPHILA</i>
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Direct selection on genetic robustness revealed in the yeast transcriptome.
No full textEvolutionary theory predicts that organisms should evolve the ability to produce high fitness phenotypes in the face of environmental disturbances (environmental robustness) or genetic mutations (genetic robustness). While several studies have uncovered mechanisms that lead to both environmental and genetic robustness, we have yet to understand why some components of the genome are more robust than others. According to evolutionary theory, environmental and genetic robustness will have different responses to selective forces. Selection on environmental robustness for a trait is expected to be strong and related to the fitness costs of altering that trait. In contrast to environmental robustness, selection on genetic robustness for a trait is expected to be largely independent of the fitness cost of altering the trait and instead should correlate with the standing genetic variation for the trait that can potentially be buffered. Several mechanisms that provide both environmental and genetic robustness have been described, and this correlation could be explained by direct selection on both forms of robustness (direct selection hypothesis), or through selection on environmental robustness and a correlated response in genetic robustness (congruence hypothesis).Using both published and novel data on gene expression in the yeast Saccharomyces cerevisiae, we find that genetic robustness is correlated with environmental robustness across the yeast genome as predicted by the congruence hypothesis. However, we also show that environmental robustness, but not genetic robustness, is related to per-gene fitness effects. In contrast, genetic robustness is significantly correlated with network position, suggesting that genetic robustness has been under direct selection.We observed a significant correlation between our measures of genetic and environmental robustness, in agreement with the congruence hypothesis. However, this correlation alone cannot explain the co-variance of genetic robustness with position in the protein interaction network. We therefore conclude that direct selection on robustness has played a role in the evolution of genetic robustness in the transcriptome
Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
No full textTo newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause
Still Pondering an Age-Old Question
No full textA theory of trade-offs to explain why we age has spurred 50 years of interdisciplinary research in evolution and molecular genetics
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