online publication
The GENETICS journal, published by the Genetics Society of America, has issued a statement which I think will soon be followed by many other similar publications. There will not be a print version of the journal anymore. Instead, it will all be online, in both HTML and PDF formats. Below is the statement in full:
Genetics, Vol. 183, 1203, December 2009, Copyright © 2009
doi:10.1534/genetics.109.112037
Presenting GENETICS: Honoring the Past, Embracing the Future
Mark Johnston, Editor-in-Chief, Tracey DePellegrin Connelly, Executive Editor, Sherry Marts, Executive Director, Genetics Society of America and Fred Winston, President, Genetics Society of America
THIS is the last “hard copy” issue of this journal. After much research and discussion, the GSA Board of Directors has decided to make GENETICS an online-only journal, effective January 2010. This change will not affect our editorial process or the journal’s content.
We admit to some sadness in reporting this turn of events because we will miss having these volumes lying on our desks, tempting us to flip through their pages. But the increasing cost of print publication and the falling usage of the print journal demands this action. Printing and mailing costs for GENETICS approached $500,000 last year, while the number of print subscribers dropped substantially. Simply put, the GSA and the journal have been subsidizing a smaller number of print subscribers at a steeply increasing cost per subscription.
The significant advantages of electronic publishing enable this course of action. Online publishing makes sense in large part because of changes that have accumulated during recent years in the prescription and process of scientific publishing and in the journal itself. For example, the August 2009 issue featured our first article PDFs with links to WormBase objects, such as gene names, alleles, and proteins, providing the community with a valuable resource and enhanced article content. This type of advance is possible only in the electronic environment. We expect this to be among the first of many collaborations with model organism databases.
As more journal articles include online-only features, such as supplemental data, the online journal has become the journal of record. Journal content is increasingly being distributed via other platforms, such as RSS feeds, and we foresee other novel means of distribution in the near future. A majority of our readers are now comfortable with the online version of the journal and access articles exclusively online; most librarians are now confident in the stability and reliability of the online archive. And librarians will appreciate the decreased demand for their shelf space.
What does this change mean to our constituents—readers, authors, GSA members, and libraries? The journal will remain, in large part, the same. We will continue to publish 12 issues in three volumes each year. Articles will still bear DOIs and page numbers and will be available online in HTML and PDF format. We will offer print-on-demand service for individual articles and article collections (e.g., reviews, specific topic areas, all articles published by an author) for those authors and readers who want high-quality reprints. And the online journal will continue to feature appealing covers.
One advantage to authors is that charges for color figures will be eliminated. And, as online technology continues to advance at a rapid pace, we will be able to invest in better ways to present authors’ articles and the supplemental information that supports them. Another consequence of the cost savings that the journal will realize is that we will not have to raise subscription prices next year. This should help us to maintain our subscription base while simultaneously supporting our library partners.
It seems clear that, for the long-term, economic restraint coupled with innovative methods of disseminating scholarly information is the path forward for the library community and for scientific societies. We are decisively embarking on that path.
Oxford at Said Seminar Series: Ageing
I attended a seminar on Monday (February 1, 2010) at Oxford’s Said Business School. There were three speakers (see the brochure below). One of the striking points I picked up from there was the relatively small amount of funding that is actually being allocated for ageing research. And this is not only true for the UK, but also in America. It is disappointing to realise that government ministers and/or policymakers do not pay enough attention (or even disregard) ageing as one of the important challenges for the future.
Linda
Today, Dame Linda Partidge will give a talk. I’m quite excited to see and listen. If you do not know her, visit the Royal Society, and watch her Croonian Prize Lecture on the new biology of ageing.
“She holds the Weldon Chair of Biometry at UCL and is director of the UCL Institute of Healthy Ageing. She is the recipient of many awards, most recently the Darwin Medal from the Linnean Society, and was awarded a CBE for services to evolutionary biology.”
Her research group aims to discover genes and mechanisms that determine the rate of ageing. They collaborate with other laboratories to examine if these processes show evolutionary conservation. Most of their work is conducted with the tiny fruitfly Drosophila melanogaster in comparison with other model organisms such as the worm and the mouse.
Her lab has been investigating dietary restriction (DR) for a long time, in relation to ageing (more specifically, the insulin signaling pathway). Dietary restriction promotes longevity but impairs fecundity (the capacity to produce offspring) in many organisms. Linda and her colleagues recently found out that when the amino acids in a diet are fine-tuned, lifespan can be increased without loss of fecundity — at least in fruitflies.
cloning success
We have been doing a cloning experiment for the longest time ever. After several attempts, we have finally succeeded today. I guess this is something to celebrate tonight, Christmas Eve. Happy holidays to all!
exponential relationship between DNA-end binding activity and maximum longevity
In a recent study published in the journal Mechanisms of Ageing and Development, Antonello Lorenzini and colleagues observed a novel relationship between the capacity of nuclear proteins to bind DNA ends and the longevity of mammalian species. This activity increases 100 fold from mouse to man and appears to be correlated with increased levels of Ku and DNA-PKcs.
Below is the introduction of their paper:
“In mammals, species lifespan can vary by more than 100 fold (shrew 2 years, bowhead whale 211 years). Despite considerable research, the cellular mechanisms that make this variation possible remain unclear. Assuming the simplest underpinning of these mechanisms, several predictions can be made. First, they likely impact fundamental processes. Second, they would be expected to be reflected by structural differences between species at the cellular level. Furthermore, these differences would be predicted to approximate the differences in observed lifespan in magnitude and to correlate independently with lifespan. As a tool to investigate these mechanisms, we have developed a series of skin fibroblast cell lines derived from mammalian species with a wide variation in lifespan. Using these lines, we have previously shown that the reported dependence of replicative capacity on longevity (Rohme, 1981) is most likely due to differences in body mass, which is itself correlated with longevity (Lorenzini et al., 2005). Therefore, comparative studies of longevity must address the influence of body mass. In the above and present analysis we used maximum species longevity and mean adult body mass from fully authenticated sources and followed published recommendations for comparative studies on longevity (Speakman, 2005). In the present study, we have examined these lines for their DNA break recognition capacity and telomere length. The results of this examination reveal a robust correlation between lifespan and DNA break recognition but little correlation with telomere length.”
a = microgram of DNA-binding protein necessary to bind 50% of the 32P-labeled probe of linear DNA
Article Source:
Significant correlation of species longevity with DNA double strand break recognition but not with telomere length
by
Antonello Lorenzini, F. Brad Johnson, Anthony Oliver, Maria Tresini, Jasmine S. Smith, Mona Hdeib, Christian Sell, Vincent J. Cristofalo, and Thomas D. Stamato
in
Mechanisms of Ageing and Development
Volume 130, Issues 11-12, November-December 2009, Pages 784-792
References Cited Above:
PDF (128 K) | View Record in Scopus | Cited By in Scopus (13)amino acid imbalance explains lifespan extension by dietary restriction in fruitflies
A study by Richard Grandison, Matthew Piper, and Linda Partridge (Nature advance online publication 2 December 2009 | doi:10.1038/nature08619) has identified the nutrients producing the responses of lifespan and fecundity to dietary restriction (DR) in the fruitfly Drosophila.
“Adding essential amino acids to the DR condition increased fecundity and decreased lifespan, similar to the effects of full feeding, with other nutrients having little or no effect. However, methionine alone was necessary and sufficient to increase fecundity as much as did full feeding, but without reducing lifespan. Reallocation of nutrients therefore does not explain the responses to dietary restriction. Lifespan was decreased by the addition of amino acids, with an interaction between methionine and other essential amino acids having a key role. Hence, an imbalance in dietary amino acids away from the ratio optimal for reproduction shortens lifespan during full feeding and limits fecundity during dietary restriction.”
“Amino acids that are not used in reproduction in the flies could shorten lifespan through metabolic costs associated with their removal; through consequent damage, for instance to the excretory malpighian tubules; or through other physiological responses.”
“… our results imply that in mammals the benefits of dietary restriction for health and lifespan may be obtained without impaired fecundity and without dietary restriction itself, by a suitable balance of nutrients in the diet.”
The image below is my own version of what I saw in their paper. Grey = Dr + amino acids. Red = fully fed. Blue = Dr.
Can we intervene in human ageing?
In a paper entitled “Can we intervene in human ageing?,” Richard Faragher and colleagues posed two obvious questions: what is ageing and why study ageing. Theycited Strehler and Mildvan (ref. 8) for the generally accepted definition of ageing as a process that is: universal (i.e. all members of a population of organisms will show it, which distinguishes ageing from infectious disease); progressive (the process is continual and incremental rather than sudden as in the case of ‘programmed’ organismal death or suicidal reproduction); intrinsic (this distinguishes ageing from death due to outside events); and degenerative (this captures the idea that ageing is associated with both increasing chances of mortality but also an increasing level of morbidity).
They mentioned some examples of interventions: (a) intervention in progeroid syndromes and (b) intervention in the ageing immune system.
heritability of longevity in the common gull
Common gulls (Larus canus) are long-lived migratory birds that breed in colonies. Jon brommer and colleagues studied 3986 common gulls over a 34-year period, and found an overall dramatic senescent decline in late life. They observed that annual fitness is heritable and that individuals vary in their rates of ageing. However, counter to theoretical expectation, there was no evidence to support a heritable component to the variance in the rates of senescence.
“Increases in the among-individual (permanent environment) and residual variance components initiate an increase in the total phenotypic variance for annual fitness with age. This suggests that older birds are more sensitive to environmental effects, and that old age causes an overall pattern of declining h(2) of annual fitness. Our findings suggest that individual-specific factors do have a role in determining the rate of senescence in this population, but that additive genetic variance for the rate of senescence is either absent or small.”
introduction of a normal human chromosome 8 corrects Werner Syndrome cells
Kentaro Ariyoshi and colleagues successfully introduced a normal human chromosome 8 into Werner Syndrome (WS) cells(fibroblasts) immortalized by expressing a human telomere reverse transcriptase subunit (hTERT) gene. In their study (published in the Journal of Radiation Research), they demonstrated that the abnormal WS cellular phenotypes like sensitivity to 4-nitroquinoline-1-oxide (4NQO) and hydroxyurea (HU), and chromosomal radiosensitivity at G(2) phase can be corrected by expression of the WRN gene upon introduction of a chromosome 8 via microcell fusion. Their results provide more evidence that the multiple abnormal WS phenotypes (clinical, cellular, and chromosomal) are derived from a primary, but not secondary, defect in the WRN gene.
flies fed an “anti-Atkins” low protein diet live longer
Researchers at the Buck Institute are studying the regulation of mitochondrial genes in the fruitfly Drosophila melanogaster in relation to ageing and lifespan. They are trying to understand how mitochondrial function relates to diet and energy metabolism, specifically the molecular mechanisms responsible for organismal longevity and lifespan extension.
It is well known that mitochondrial function declines with age in many biological organisms. “Our study shows that dietary restriction can enhance mitochondrial function hence offsetting the age-related decline in its performance,” said Buck faculty member Pankaj Kapahi, lead author of the study. Their study presented a genome-wide study of the effect of dietary restriction on certain proteins. They reported that while there is a reduction in protein synthesis globally with a low protein diet, the activity of specific genes involved in generating energy in the mitochondria are increased.
They particularly studied the d4EBP protein, which is involved in a molecular signaling pathway that mediates cell growth in response to nutrient availability called TOR (target of rapamycin). They observed that when the activity of d4EBP is genetically “knocked out,” flies did not live longer, even when fed the low protein diet. When the activity of d4EBP was enhanced, lifespan was extended, even when the flies ate a rich diet.
The research calls into question the health benefits of high-protein diets. The long-term impacts of such diets have not been examined in humans. “In flies, we see that the long-lived diet is a low protein diet and what we have found here is a mechanism for how that may be working,” Kapahi said. The study provides a significant advance in understanding the role of 4EBP, a downstream molecular target of TOR, which mediates a switch in metabolism to extend lifespan.
A recent study published in Nature has demonstrated that feeding rapamycin (an antibiotic) to mice inhibited TOR and extended their lifespan.
Below is the summary of their paper published in Cell (October 2, 2009):
Dietary restriction (DR) extends lifespan in multiple species. To examine the mechanisms of lifespan extension upon DR, we assayed genome-wide translational changes in Drosophila. A number of nuclear encoded mitochondrial genes, including those in Complex I and IV of the electron transport chain, showed increased ribosomal loading and enhanced overall activity upon DR. We found that various mitochondrial genes possessed shorter and less structured 5′UTRs, which were important for their enhanced mRNA translation. The translational repressor 4E-BP, the eukaryotic translation initiation factor 4E binding protein, was upregulated upon DR and mediated DR dependent changes in mitochondrial activity and lifespan extension. Inhibition of individual mitochondrial subunits from Complex I and IV diminished the lifespan extension obtained upon DR, reflecting the importance of enhanced mitochondrial function during DR. Our results imply that translational regulation of nuclear-encoded mitochondrial gene expression by 4E-BP plays an important role in lifespan extension upon DR.
