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) fibroblasts immortalized by expressing a human telomere reverse transcriptase subunit (hTERT) gene. In their study (published in the Journal of Radiation Reseasch), they demonstrated that the abnormal WS phenotypes including cellular sensitivities to 4-nitroquinoline-1-oxide (4NQO) and hydroxy urea (HU), and chromosomal radiosensitivity at G(2) phase can bee corrected by expression of the WRN gene mediated by introducing a chromosome 8. This indicates that those multiple abnormal WS phenotypes 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.
bonfire night
Right, this blog has been silent for a month. Let’s keep the ball rolling, shall we. Detours will come upon here from time to time . Today, the excitement is all about bonfire night …
“Indulge your pagan and your pyromaniac urges with the UK’s greatest bonfire bacchanale … The Bonfire Societies will signal the start of the processions by racing barrels of burning tar down the High Street at 6.30pm, after which the whole town seems to parade past in a variety of outlandish outfits. Guy Fawkes gets his comeuppance from around 22h, when bonfires, effigies and several tons of fireworks go up in smoke at five separate fire sites.”
(courtesy of M&MSmith)
another ageing conference in birmingham
I was in Birmingham a few days ago to attend another ‘ageing’ conference. There were several presentations from the Disconnected Mind project. I quite baffled by the extent of their work: psychology, sociology, neuroscience, physiology, histology, genetics. All on the ageing brain and cognitive decline.
when it doesn’t work
I think most people who work in an experimental research lab recognise that not all experiments yield good results. And so today, I found out that the RTS 100 synthesis I did yesterday was of no good at all. What I saw in my gels were all alike, including the GFP vector.
Instead of sulking, I think I shall make myself happy by having a pint of ice cream after a sumptuous dinner. Have a nice evening to you all. I leave you with a clever sandwich:
Why study ageing?
I had an interesting discussion with non-science friends last week about ageing research. So, why study ageing? I shall get back on this … in the meantime, let us revisit the original position paper on human aging in 2002 by S. Jay Olshansky, Leonard Hayflick, and Bruce Carnes. Below is the introduction:
“In the past century, a combination of successful public health campaigns, changes in living environments, and advances in medicine have led to a dramatic increase in human life expectancy. Long lives experienced by unprecedented numbers of people in developed countries are a triumph of human ingenuity. This remarkable achievement has produced economic, political, and societal changes that are both positive and negative. While there is every reason to be optimistic that continuing progress in public health and the biomedical sciences will contribute to even longer and healthier lives in the future, a disturbing and potentially dangerous trend has also emerged in recent years. There has been a resurgence and proliferation of health care providers and entrepreneurs who are promoting anti-aging products and lifestyle changes that they claim will slow, stop, or reverse the processes of aging. Even though in most cases there is little or no scientific basis for these claims (1), the public is spending vast sums of money on these products and lifestyle changes, some of which may be harmful (2). Scientists are unwittingly contributing to the proliferation of these pseudo-scientific anti-aging products by failing to participate in the public dialogue about the genuine science of aging research. The purpose of this document is to warn the public against the use of ineffective and potentially harmful anti-aging interventions, and provide a brief but authoritative consensus statement from 51 internationally recognized scientists in the field [see (104)] of what we know and do not know about intervening in human aging. What follows is a list of issues related to aging that are prominent in both the lay and scientific literature, and the consensus statements about these issues that grew out of debates and discussions among the 51 scientists associated with this paper.”
Sci. Aging Knowl. Environ., 19 June 2002
Vol. 2002, Issue 24, p. pe9
[DOI: 10.1126/sageke.2002.24.pe9]
ageing in crickets (male versus female)
A recent study by Alexei Maklakov and colleagues showed differences in ageing between male and female crickets. They observed “dramatic, qualitative differences in age-dependent reproductive performance trajectories and patterns of reproductive ageing in the cricket Teleogryllus commodus.“
—Female fecundity declined with age as predicted by the evolutionary theory of aging.
—In contrast, males showed increasing calling effort with age.
“Our results are consistent with two non-exclusive mechanisms: either sexual selection has resulted in delayed aging by promoting late-life performance in males, or sexual selection has favoured an age-dependent increase in male reproductive effort that counteracts (and obscures) concomitant deterioration in reproductive capacity (i.e. aging). Our findings thus suggest that, as a consequence of sexual selection, the signal of reproductive aging may often be weaker in males than in females.”
Aging Cell
Volume 8 Issue 3, Pages 324 – 330
Published Online: 9 Apr 2009
Below is Figure 2, showing the relationship between lifespan and age-dependent female egg-laying (a, in eggs per week) or male calling (b, in seconds calling per night). Red lines indicate median adult lifespan and blue lines indicate maximum predicted adult lifespan for each sex, from a capture–recapture study of adults in the wild at the source site where collections were made. (c, d) Age-specific trajectories of egg-laying (females, c) and calling effort (males, d) for cohorts of individuals of different lifespans (indicated in blue numbers next to the trajectory curves).
Silverville
There is a TV series entitled Silverville, from the BBC and The Open University. It tells stories from a retirement village in Milton Keynes called Lovat Fields.
The 26 year old Bart Corpe describes his arrival:
“I arrived in Lovat Fields and to my surprise it was not like a nursing home at all. It was a very modern facility with brand new apartments, a gym, a Jacuzzi, snooker table, pool table and even a café/bar serving a pint at £1.75! These old folk haven’t got it that bad I thought and things were looking up.
After meeting a number of the residents I started to realise they were no different from anyone else, they are just people after all. You have your jokers, your serious people, your drinkers and non-drinkers, the people that like to stay active and sociable, to those who, by all accounts would rather be left alone. I was enjoying the company of the residents and was fascinated to listen to their stories from their pasts, of the lives they had led and the experiences they could share, especially personal stories of the war.”
It is a fact, for the moment, that we are all going to grow old. And some of us (if not all) will probably end up in a place known to many as “old people’s home” or “nursing home” or a ” retirement village”. How did we get into something like this? Why go to these specific places (enticingly described as purpose-built communities offering security, companionship and independence for the over 55s) when you’re old (and, presumably, dying)? How did we end up having a choice to leave (or not) our homes and move (or not) to such places? Why not stay in the same permanent address until we die? The TV series may not satisfy my curiosity but it might help to discover how “old people” live their lives in a retirement village.
Here’s a glimpse from Silverville’s About The Series page:
“Retirement communities are one option for our rapidly aging population; residents can buy their own apartment or bungalow, share the ownership, rent, or be funded by social services and there’s care on hand if they need it.
The village – which cost more than £30 million to build – has a shop, hairdressers, gym, bar, restaurant and a packed schedule of leisure activities and events.
As the government puts increasing emphasis on promoting independence for older people, offering them choices, and improving their quality of life. Retirement villages could be the answer for some.“
I’m trying to recall a recent movie I saw this year … brb …
Rapamycin increases lifespan in mice
Lynne Cox wrote an article on the BSRA News Section about the recent Nature paper by David Harrison and colleagues: Rapamycin fed late in life extends lifespan in genetically heterogeneous mice; Nature 460, 392-395 (16 July 2009); doi:10.1038/nature08221; Published online 8 July 2009. This paper was also reported in a news item by Matt Kaeberlein and Brian Kennedy also within that Nature issue.
Here’s a portion of Lynne’s article:
“Rapamycin (C51H79NO13), now more correctly known as sirolimus, is a macrolide antibiotic produced by the soil bacterium Streptomyces hygroscopicus, initially found on Easter Island in the South Pacific. Perhaps this is one of the reasons why the media hype surrounding this story grew to such proportions: Easter Island is renowned for its mysterious monoliths, and it might be easy for the superstitious to find some sort of connection between this mystery and the so-called “elixir of youth”. More prosaically, the biosynthetic pathway of rapamycin, mediated by a series of bacterial Rap genes, is known and the drug is manufactured commercially, disconnecting it from its ‘mysterious’ origins.”
This study on mice lifespan is all good. However, it has to be reiterated — rapamycin is a potent immunosuppressant.
Twiggy and Ageing
I cannot avoid mentioning that Twiggy, the so called “The Original Supermodel” is turning 60. And it is without doubt that she still remains in the limelight and continues to be a darling of the press. She recently published a book on ageing, for women above 40. I reckon this book is partly autobiographical too. What is inside the book intrigues me. Check her out.
