Narrow Results

Penna's bit-string model of biological ageing due to the accumulation of deleterious mutations is generalized to allow for more than one disease per year. The results remain qualitatively unchanged except for a more complicated non-monotonic approach to equilibrium. We also look at "mutational meltdown", the extinction of the whole population if all mutations are deleterious and heritable, and why the Penna model can escape this extinction. No dependence on population size is found for mutational meltdown, with up to 10⁸ individuals.

Using computer simulations of a bit-string model for age-structured populations, we found that sexual selection of older males is advantageous, from an evolutionary point of view. These results are in opposition to a recent proposal of females choosing younger males. Our simulations are based on findings from recent studies of polygynous bird species. Since secondary sex characters are found mostly in males, we could make use of asexual populations that can be implemented in a fast and efficient way.

How to make value-based care a reality?

Impactful interventions to maximise healthspan.

Viral hepatitis in Arkhangai: How Asia’s first micro-treatment program’s successes can be leveraged to treat a “silent killer”.

The long-suffering challenge of vaccination.

Sirtuins comprise a family of enzymes implicated in the determination of organismal lifespan in yeast and the nematode. Human sirtuin SIRT1 has been shown to deacetylate several proteins in a NAD⁺-dependent manner. It is reported that SIRT1 regulates physiological processes including senescence, fat metabolism, glucose homeostasis, apoptosis, and neurodegeneration. In general, SIRT1 has initially been thought to represent an exclusive nuclear protein. However, depending on the cell lines and organisms examined, a partial or temporary cytoplasmic localization was observed in murine pancreatic beta cells and neonatal rat cardiomyocytes. Since SIRT1 deacetylates both histone and nonhistone-proteins, such as a number of transcription factors, changes in subcellular localization probably play a role in the regulation of its function. In the present studies, we investigated the subcellular localization of SIRT1 in response to growth factor deprivation in African green monkey SV40-transformed kidney fibroblast cells (COS-7). Using SIRT1-EGFP fluorescence reporter, we found that SIRT1 localized to nucleus in physiological conditions. We devised a model enabling cell senescence via growth factor deprivation and found that SIRT1 partially translocated to cytosol under the treatment, suggesting a reduced level of SIRT1 activity. We found PI3K/Akt pathway was involved in the inhibition of SIRT1's cytosolic translocation, because inhibition of these kinases significantly decreased the amount of SIRT1 maintained in nucleus. Taken together, we demonstrate that growth factor deprivation induces cytosolic translocation of SIRT1, which suggests a possible connection between cytoplasm-localized SIRT1 and the aging process and provides a new application of single molecule fluorescence imaging of the molecule events in living cells.

The effects of superoxide dismutase on aging were tested using two differt experimental approaches. In the first, replicated populations with postponed aging were compared with their controls for frequencies of electrophoretic alleles at the SOD locus. Populations with postponed aging had consistently greater frequencies of the allele coding for more active SOD protein. This allele was not part of a segregating inversion polymorphism. The second experimental approach was the extraction of SOD alleles from different natural populations followed by the construction of different SOD genotypes on hybrid genetic backgrounds. This procedure did not uncover any statistical effect of SOD genotype on longevity or fecundity. There were large effects on longevity and fecundity due to the family from which a particular SOD genotype was derived. To detect the effects of SOD genotypes on longevity with high probability would require a ten-fold increase in the number of families used.