DRUSE (by RALPH)

I’ve just been to an event up in Keele last Friday. And I was very enthusiastic in explaining what I do to everyone I met there. But every time I tell them I’m working on ageing, somewhere along the conversation the “anti-ageing cream” always gets mentioned. It never fails. What’s the fuss with this anti-ageing cream? Why does it seem that almost everyone is talking about it?

anti-ageing cream

fountain of youth

In the journal DNA Repair (July 2008), Mark O’Driscoll and Penny Jeggo review how double strand breaks (DSBs) arise and discuss the multiple pathways that impact upon the response to DSBs.

Below is the abstract of their paper:

A network of DNA damage response (DDR) mechanisms functions co-ordinately to maintain genomic stability and ensure cellular survival in the face of exogenous and endogenous DNA damage. Defects in DDR pathways have been identified in a range of human disorders, collectively classified as DDR-defective syndromes. A common feature of these syndromes is a predisposition to cancer demonstrating the importance of the DDR in cancer avoidance. How the DDR mechanisms serve to maintain genomic stability has been the predominant focus of research into their function. However, many DRR-defective syndromes are also characterised by impaired development demonstrating broader roles for the DDR mechanisms. Microcephaly, representing reduced brain size, is a feature common to a diverse range of DDR-defective disorders. Microcephaly is most likely caused by loss (increased cell death) or failure of the developing neuronal stem cells or their progenitors to divide suggesting a fundamental role for the DDR in maintaining proliferative potential in the developing nervous system. Currently, it is unclear why the DDR proteins should be more important during neuronal development compared with the development of other tissues or why the embryonic brain is more sensitive than the adult brain. Here, we overview the DDR-defective disorders in the context of microcephaly and discuss a model underlying this striking phenotype.

DNA Repair (Volume 7, Issue 7, 1 July 2008, Pages 1039-1050)

The group of Ying Li reported on the effects of sirtuin SirT1 on neurons. Here’s their abstract:

Sirtuins are known to protect cells and extend life span, but our previous studies indicated that S. cerevisiae Sir2 can also increase stress sensitivity and limit life-span extension. Here we provide evidence for a role of the mammalian Sir2 ortholog SirT1 in the sensitization of neurons to oxidative damage. SirT1 inhibition increased acetylation and decreased phosphorylation of IRS-2; it also reduced activation of the Ras/ERK1/2 pathway, suggesting that SirT1 may enhance IGF-I signaling in part by deacetylating IRS-2. Either the inhibition of SirT1 or of Ras/ERK1/2 was associated with resistance to oxidative damage. Markers of oxidized proteins and lipids were reduced in the brain of old SirT1-deficient mice, but the life span of the homozygote knockout mice was reduced under both normal and calorie-restricted conditions. These results are consistent with findings in S. cerevisiae and other model systems, suggesting that mammalian sirtuins can play both protective and proaging roles.

Sourcel — Cell Metabolism, July 2008

http://www.cellmetabolism.org/content/article/abstract?uid=PIIS1550413108001484

A new study has been reported in Science magazine about eusociality. Eusocial behavior, exemplified by social insects, is characterized by individuals helping to rear siblings rather than their own offspring.

“Close relatedness has long been considered crucial to the evolution of eusociality. However, it has recently been suggested that close relatedness may be a consequence, rather than a cause, of eusociality. We tested this idea with a comparative analysis of female mating frequencies in 267 species of eusocial bees, wasps, and ants. We found that mating with a single male, which maximizes relatedness, is ancestral for all eight independent eusocial lineages that we investigated. Mating with multiple males is always derived. Furthermore, we found that high polyandry (>2 effective mates) occurs only in lineages whose workers have lost reproductive totipotency. These results provide the first evidence that monogamy was critical in the evolution of eusociality, strongly supporting the prediction of inclusive fitness theory.”

Science 30 May 2008:

Vol. 320. no. 5880, pp. 1213 - 1216

Ancestral Monogamy Shows Kin Selection Is Key to the Evolution of Eusociality

William Hughes, Benjamin Oldroyd, Madeleine Beekman, Francis Ratnieks

[link]

The group of Gina Moore published a paper in the journal Mechanisms of Ageing and Development (April 200 on the Werner Syndrome (WS) in mice, in relation to diabetes. They examined if mutations in the Werner Syndrome protein WRN might affect metabolic response to a diabetogenic diet. They found that WRN null mice had significantly increased body weights, increased serum insulin levels, impaired glucose tolerance, and insulin resistance during 4 months of eating the diabetogenic die. Their results suggest that WRN null mice have impaired glucose homeostasis and fat metabolism, and may be a useful model to investigate metabolic conditions associated with aging.

[link]

After a month of inactivity, Druse is back.

In a recent issue of Nature (Volume 451, Pages 535-540, 31 January 2008), Eran Segal and his group presented a thermodynamic model of the segmentation gene network in Drosophila. The model computes expression patterns as a function of cis-regulatory sequence and of the binding-site preferences and expression of participating transcription factors. The accuracy of the model demonstrates that positional information is encoded in the regulatory sequence and input factor distribution.

Click here for the [link], and here for the pdf — Eran Segal

…

On Nature’s Web Focus on Drosophila (November 2007), there was a review by John Lis on imaging polytene chromosome in larval salivary glands. Figure 3 shows a glimpse of what we can expect to see using recent advances in cell imaging.

“The ability to attach green fluorescent protein (GFP) and related fluorescent tags on chromosomal proteins has added a vital temporal dimension to the analysis of protein–DNA and protein–protein interactions in nuclei and on chromosomes. Expression of GFP-tagged proteins in mammalian cell lines allows the dynamics of transcription factors and chromatin components to be examined in nuclei in real time(16, 17). Fluorescence recovery after photobleaching (FRAP) experiments additionally reveal the dynamics of a nuclear protein within an arbitrarily chosen nuclear region(18), or at a specific transgenic locus containing tandemly repeated genes(16). Examination of specific, native gene loci requires more sensitivity and higher-resolution views of interphase nuclei. The giant interphase nuclei of Drosophila polytene tissue provide both the sensitivity and effective resolution to detect signals from specific chromosomal loci(3).”

[link] Nature 450, 198-202 (8 November 2007)

A paper by the group of Jefferson Perry reported crystallographic structures of the human WRN exonuclease (WRN-exo). Their data provided evidence that human WRN-exo is a member of the DnaQ family of 3′ - 5′ exonucleases. This family is known to include the bacterial KF-exo as well as the the plant Arabidopsis thaliana protein At5G06450.

[link]