bluuebunny/crossref_metadata_2025 huggingface dataset:
Vive la France: Minister announces budget and priorities for new aging institute
Authors: Mertl Melissa
Published: August 2003

The outlines of a new French institute for aging research are taking shape. After more than 8 months of discussion, the French minister of research announced in late October that a new Longevity Institute "without walls" will provide 21 million French francs (about US$3M) next year to fund and organize research on genetics, sensory loss, animal models of aging, and assisted-living technologies.

Citing an oncoming epidemic of aging, research minister Roger-Gérard Schwartzenberg explains the need to better coordinate aging research in the country. "The life expectancy [of the French] is among the highest in the world," he says. By 2011, France will have more people over the age of 60 than under the age of 20. Half the French girls born today are expected to become centenarians, he adds, and an increase in longevity could place the publicly funded health care and pension systems in jeopardy.
Étienne-Émile Baulieu, a hormone and reproduction specialist who is vice president of the French Academy of Sciences, led the proposal for the new federal aging initiative and has been named its future coordinator. The leaders of the projects listed as priorities for funding have just learned of the minister's intentions themselves and "haven't started to bargain yet" for shares of the financial pie, Baulieu says.

Epidemiologist Philippe Amouyel, who directed the collection of serum and plasma samples for the so-called three city study expected to lie at the heart of the new national aging initiative, says he was "thrilled" to hear Baulieu's announcement. Almost 10,000 people over the age of 65 living in the vicinity of three major cities in France are participating in the longitudinal study, which tracks about 500 variables for each individual. Next year, researchers will start using the data to seek genes and other biological markers associated with the ailments of old age, such as stroke, dementia, and hypertension.

The new national institute has targeted other areas as well. It is prioritizing research on disorders of vision, hearing, and balance and plans to create a national breeding center and tracking repository for animals used in aging research. In addition, the institute intends to support research on technology that can help the elderly live more comfortable and healthy lives. The fabled goal of retirement at age 60 with a full pension and a French country house might need a petit revision; Schwartzenberg describes the creation of "smart homes" that might have gadgets not only to assist with independent living but also to monitor an elderly person's cardiorespiratory function, cognition, and ability to move around.

As a new generation of French citizens vie to beat the longevity record set by their compatriot Jeanne Calment (who died in 1997 at the age of 122), research leaders in the country will be toiling to understand--and put a shine on--those golden years.

--Melissa Mertl

Further Reading

French Ministry of Research
http://www.recherche.gouv.fr/english
Dieting Dwarves Live It Up
Authors: Beckman Mary
Published: August 2003

Two longevity pathways affect growth and metabolism in similar ways, and researchers have wondered for years whether the two routes coincide. A new study hints that these roads might not even lie on the same page of the atlas. Calorie restriction further extends the lives of mice already renowned for longevity due to a mutation in the
Prop-1
gene. The results, reported in the 22 November issue of
Nature
, suggest that the two pathways don't overlap and indicate that researchers could travel a long way before they reach the maximum life-span of mice and perhaps humans.
Running Low But Long: Mutation in energy production machinery extends life in worms (Oxidative stress)
Authors: Beckman Mary
Published: August 2003

Some people think stress kills--and the image of the businessman nearly popping his jugular isn't all they're thinking about. Researchers have long pursued the connection between oxidative stress and aging. While generating the adenosine triphosphate that powers the cell, mitochondria also give birth to the byproduct superoxide, a highly reactive oxygen radical that can damage other molecules. To protect the cell, resident enzymes turn superoxide into the slightly less obnoxious peroxide and then into innocuous water--but they don't neutralize it all. Some researchers propose that the havoc wreaked by these reactive oxygen species (ROS) promotes aging (see
"The Two Faces of Oxygen"
), based in part on observations that an antioxidant drug and mutations that disrupt global energy-producing activities can extend worm and yeast life-spans, respectively. Although no one has clearly shown that ROS shorten life, circumstantial evidence is mounting. Now, researchers add another piece of data to the pile: A mutation in a gene that normally promotes ROS production lengthens life-span in worms.

In their search for a connection between oxidative damage and aging, Hekimi and colleagues generated a collection of
Caenorhabditis elegans
strains that carried random mutations and identified some with extended life-spans. Further analysis revealed that one of them carries an alteration in the gene that encodes the iron sulfur protein (ISP-1). ISP-1 is a go-between for two proteins in the mitochondrial energy generator as well as a culprit in ROS production: ISP-1 passes electrons from cytochrome b to cytochrome c and can create superoxide in the process. Worms that harbor the mutation in
isp-1
live up to twice as long as normal, and their physiology differs in other ways as well. They lay fewer eggs, defecate more slowly--and consume about half the oxygen as do wild-type animals. The latter result suggests to the researchers that the mutant worms make fewer ROS; however, the team didn't directly measure ROS production, and other phenomena could also explain the findings.

More work is necessary to nail down exactly how changes in
isp-1
lead to its newly discovered life-extending power, but the new addition to the collection of genes that affect oxidative damage and aging might help scientists understand how these phenomena are connected.

--Mary Beckman; suggested by Matt Kaeberlein

J. Feng, F. Bussière, S. Hekimi, Mitochondrial electron transport is a key determinant of life span in
Caenorhabditis elegans.
Dev. Cell
1
, 633-644 (2001).
[Abstract]
[Full Text]
Stay Mellow, Stay Young
Authors: Seydel Caroline
Published: August 2003

Mutations in single genes can extend the life-span of several model organisms, but the picture of whether and how those genes contribute to longevity in mammals remains muddy. New work links proteins involved in worm and mammalian aging and also ties in reactive oxygen species, destructive molecules that are thought to contribute to aging in a variety of creatures. Although the growing number of similar aging themes among diverse organisms is clarifying some general ideas, the details--and variations--are turning out to be a complex business.
The Werner Syndrome Helicase-Nuclease--One Protein, Many Mysteries
Authors: Fry Michael
Published: August 2003

Werner syndrome
(WS) is an autosomal recessive condition characterized by an early onset of age-related symptoms that include ocular cataracts, premature graying and loss of hair, arteriosclerosis and atherosclerosis, diabetes mellitus, osteoporosis, and a high incidence of some types of cancers. A major motivation for the study of WS is the expectation that elucidation of its underlying mechanisms will illuminate the basis for "normal" aging. In 1996, the gene responsible for the syndrome was positionally cloned. This advance launched an explosion of experiments aimed at unraveling the molecular mechanisms that lead to the WS phenotype. Soon thereafter, its protein product, WRN, was expressed, purified, and identified as a DNA helicase-exonuclease, a bifunctional enzyme that both unwinds DNA helices and cleaves nucleotides one at a time from the end of the DNA. WRN was shown to interact physically and functionally with several DNA-processing proteins, and
WRN
transgenic and null mutant mouse strains were generated and described. The substantial number of excellent reviews on WRN and WS that were published in the past 2 years (
1
-
7
) reflects the rapid pace of advances made in the field. Unlike those comprehensive articles, this review focuses on the biochemistry of the WRN protein and some aspects of its cell biology. Also considered are the putative functions of WRN in normal cells and the consequences of the loss of these functions in WS.
An Untwister's New Twist
Authors: Davenport R. John
Published: August 2003

Defects in helicase enzymes result in a number of diseases that mimic aspects of growing old. New work shows that a helicase implicated in one of these conditions--xeroderma pigmentosum (XP)--apparently helps hormones activate genes in addition to its well-known ability to unwind DNA. The protein's newly discovered role in hormone signaling might underlie unexplained XP symptoms.
Playful Rejuvenation: Researchers turn to music and other diversions for inspiration (People)
Authors: Davenport R. John
Published: August 2003

Donna Holmes
is skeptical of the "Grandmother Hypothesis" (see
Holmes Perspective
). But when a proponent of the theory contacted the University of Idaho researcher and suggested that the two of them didn't think that differently, Holmes worked hard to sort out the data on each side. "She sent me a vast amount of literature," says Holmes. "I'm still struggling to process all that information." When faced with such intense intellectual challenges, Holmes says she often retreats to the local bar and sits down with a margarita to focus on the problem at hand. If things get really overwhelming, however, she dons a vintage dress and a tiara.

Drive through Moscow, Idaho, on the right night and you might catch Holmes belting out Motown tunes with "The Hot Flashes." The diversion helps her set aside the challenges of studying aging and get mentally refreshed, she says: "Singing and performing just seem to require a whole different set of abilities and personality traits."

For several other scientists who study aging, creating music or venturing into the natural world brings perspective. For instance, Rudolph Tanzi, who studies Alzheimer's disease at Harvard Medical School in Boston, refreshes himself by tickling the ivories. "I just play piano and improvise on some jazz theme until I relax," he says. "It works every time." Music is more than just a diversion, however. In the '80s, Tanzi played steady gigs with Ritchie Blackmore of Deep Purple--and could even have passed up college to tour with Blackmore's new band at the time. Tanzi still records, and he intends the music from his "Quiet Mind Project" to do just what it says.

On the other side of the continent, when Caleb "Tuck" Finch of the University of Southern California in Los Angeles isn't investigating genomic regulation of aging processes, he's fiddlin' old-time music with the Iron Mountain String Band. Across the Atlantic, Adam Antebi blows the saxophone, which he says helps inspire his work on
Caenorhabditis elegans
aging and development at the Max Planck Institute for Molecular Genetics in Berlin, Germany.

Music isn't the only thing that rejuvenates researchers; others turn to the great outdoors. María Blasco of the National Center of Biotechnology in Madrid says conversations with her husband during long hikes give her "a more global view." And scuba diving gets
Simon Melov
out of a rut. Melov, of the Buck Institute for Age Research in Novato, California, also recharges himself through visits to alien landscapes by reading science fiction.

What inspires you? Add a comment to this story and share how you refresh your mind.

--R. John Davenport
Meeting Report--National Institute on Aging Workshop on the Comparative Biology of Aging
Authors: Warner Huber , Miller Richard A. , Carrington Jill
Published: August 2003

This Perspective is a summary of the Comparative Biology of Aging Workshop that was held in February 2002 by the National Institute on Aging in Bethesda, MD. Participants discussed ways to exploit similarities and differences in aging among diverse species to learn more about critical factors that affect aging and regulate life expectancy in animals. The aim of the workshop was to stimulate new approaches to understanding the molecular bases for differences in aging rates and life expectancy among species.
Long-Lived Worms
Authors: Kenyon Cynthia
Published: August 2003

View a PowerPoint presentation on
daf-2
and
daf-16
,
Caenorhabditis elegans
genes that affect worm life-span. The genes are part of an insulin/insulin-like growth factor-1 (IGF-1) pathway that also affects life-span in flies and perhaps mice.

[Presentation]
Lecture Schedule
Authors: Roach Deborah
Published: August 2003

Read one biologist's approach to planning a class on aging.

[Lecture Schedule]
Don't Pass the Buck
Authors: Pyne Solana
Published: August 2003

As the first nonprofit center for research on aging in the United States, the Buck Institute for Age Research has broken ground in more ways than one. Housed in designer buildings, an enthusiastic faculty is taking aim at diseases from Parkinson's to cancer and delving into the myriad of processes that might contribute to a creature's demise. Because the institute is only two and a half years old and has just 14 lab heads, it's too soon to tell how big a player the Buck Institute will become in the field of aging. But talented researchers, state-of-the-art technology, and generous institutional funding all bode well for its future.
How a
clk
Ticks
Authors: Davenport R. John
Published: August 2003

New work offers tantalizing clues about possible connections between life-span, DNA damage, and the health of chromosome ends. Although the newly discovered sequence of a longevity gene suggests that it controls the length of telomeres--chromosome caps that shrink each time a cell copies its DNA--the three teams that are independently studying it disagree about that potential function. Additional clues suggest that the gene has DNA-mending capabilities, which could be the key to its life-extending powers.
Puzzling Over Research on Aging
Authors: Ghazi Arjumand
Published: August 2003

This crossword puzzle was devised by Arjumand Ghazi, a SAGE KE Scientific Advisory Board assistant. Test your knowledge of aging-related research, and have fun in the process.
Position Statement on Human Aging
Authors: Olshansky S. Jay , Hayflick Leonard , Carnes Bruce A.
Published: August 2003

Fifty-one top researchers in the field of aging collaborated to create this position paper. It describes what scientists know and do not know about intervening in human aging, and includes information on ineffective and potentially harmful anti-aging interventions. See reference (
104
) for a complete list of these scientists.
Hematopoietic Stem Cells and Aging
Authors: Fuller Jennifer
Published: August 2003

Hematopoiesis is a process by which a single cell--called a hematopoietic stem cell (HSC)--has the proliferative potential to give rise to all of the major lineages of blood and immune cells. Stem cells can undergo both symmetric division, which results in two copies of the parent stem cell, and asymmetric division, which results in self-renewal of the parent stem cell as well as production of a daughter cell that is capable of differentiating along a specific lineage. A number of different elements of HSC replication change with age, even though these transformations do not appear to result in hematopoietic deficiencies under normal circumstances. In this Perspective, the author discusses these age-related alterations.
Give Me Liberty or Give Me an Early Death
Authors: Leslie Mitch
Published: August 2003

Domestication has robbed lab mice of genes that slow aging, according to a new study. Wild mice not only outlive their lab-dwelling cousins but also show hormone concentrations associated with slower aging, gerontologists report in the July issue of
Experimental Biology and Medicine
. The results suggest that studying only lab-adapted strains of rodents might hamper understanding of the molecular mechanisms that make us grow old.
"Gero-Tech" Sprouts, But Will It Bloom?
Authors: Davenport R. John , Toy Jennifer
Published: August 2003

Companies are betting that studies of aging will reveal new routes to life-enhancing pharmaceuticals. Antiaging pills are a distant dream, in part because testing a drug for its effect on life-span is a practical impossibility and scientists haven't yet come up with a substitute measure of aging. But research on aging might yield novel ways to treat age-related disease. Along the way, private ventures are offering new resources and a variety of experiences to academic scientists.
Innate Immunity, Local Inflammation, and Degenerative Disease
Authors: McGeer Patrick L. , McGeer Edith G.
Published: August 2003

The brain lesions associated with Alzheimer's disease (AD), which are referred to as neurofibrillary tangles and senile plaques, are characterized by the presence of a broad spectrum of inflammatory mediators. Surprisingly, these mediators, which include complement proteins, inflammatory cytokines, prostaglandins, and acute phase reactants such as C-reactive protein and amyloid P, are produced by resident brain cells, including neurons. Although secondary to the fundamental pathology caused by the presence of tangles and plaques, there is strong evidence that inflammation exacerbates the neuronal loss. In particular, AD lesions show evidence of self-attack by the complement system--a part of the immune system that normally functions to rid the body of invading pathogens. However, the lesions are devoid of significant T cell infiltration, a hallmark of an inflammatory immune response, and antibodies. We define this phenomenon as autotoxicity to distinguish it from classical autoimmunity, in which the body raises antibodies to normal endogenous macromolecules. Locally produced inflammatory mediators have also been identified in atherosclerotic plaques, along with evidence of complement self-attack. As was previously shown for heart attacks, epidemiological evidence indicates that extended use of nonsteroidal anti-inflammatory drugs (NSAIDs) results in a reduced risk of AD. NSAIDs inhibit the production of prostaglandin inflammatory mediators, but powerful new therapeutic agents might be developed by targeting more critical inflammatory mechanisms, especially the complement system.
The Shrimps Shall Inherit the Earth
Authors: Chen Ingfei
Published: August 2003

A new report confirms that peewees outlast titans--among rodents, at least. Whereas most studies assess size at one time point or life stage, the new one tracks the rodents' weight month by month from birth to death. As a result, the work offers the first hint that body weight at an early age correlates with an animal's life expectancy.
Mitigating the Tithonus Error: Genetic Analysis of Mortality Phenotypes
Authors: Pletcher Scott D.
Published: August 2003

Summarizing an organism's age at death in terms of the mean or maximum life-span is the most popular way to describe genetic effects on aging. In this Perspective, the author describes a new study with the fly
Drosophila melanogaster
, in which another type of measure is also used: the age-dependent risk of death, or age-specific mortality. Changes in age-specific mortality reflect the underlying physiological deterioration of an organism as it ages. Thus, the author argues that these changes provide a phenotype that is ideal for the genetic analysis of aging.
Laboratory Performance Appraisal
Authors: Ottemann Karen
Published: August 2003

An important aspect of the principal investigator's job is to mentor students and postdocs and help them develop as scientists. In guiding my own lab members, I knew that it was important to give them feedback in order to build on their strengths and help improve their abilities. I found it very difficult, however, to tell lab members their good and bad points constructively. I realized that in many jobs, employees participate in annual reviews that are guided by a form that divides the expectations of a position into specific categories. I have designed a similar form geared toward students and postdocs working in the laboratory. With some modifications, it could also be adapted for technicians and undergraduates. I have found this to be a very productive way to emphasize their strengths and point out their shortcomings; it is also useful in allowing them to make suggestions and air grievances.

[Performance Appraisal Form]
Setting a Trap for Aging-Related Genes in
Drosophila
Authors: Tower John
Published: August 2003

In the October 2002 issue of

Aging Cell

,

Seroude
et al.

used an enhancer trap technique to identify
Drosophila
genes whose expression changes with age. In this Perspective, the author discusses the implications of these results, including the possibility of using the enhancer trap lines to identify biomarkers of aging.
Flies Like Us
Authors: Leslie Mitch
Published: August 2003

Although our lineage separated from theirs 500 million years ago, fruit flies are proving to be informative models for human neurodegenerative diseases. Scientists have augmented the insects with human disease-causing genes, reproducing the molecular mayhem and some of the symptoms of Parkinson's disease, Huntington's disease, and other killers. The insects are easy to genetically manipulate, get old in a hurry, and are light on the wallet, making them valuable for untangling the molecular causes of neural degeneration and screening potential treatments. Using flies carrying a gene that is defective in some Parkinson's patients, scientists have already identified a protein that suppresses the neural damage from the disease.
Of Worms, Flies, Dwarfs, and Things That Go Bump in the Night
Authors: Sonntag William E. , Ramsey Melinda M.
Published: August 2003

Studies over the past several years have found that antagonism of the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway increases life-span in
Caenorhabditis elegans
and
Drosophila
. However, a persistent problem in these studies is the fact that the genetic mutation has effects on the development of the organism as well as on reproductive function. These effects act as potential confounding variables that complicate the interpretation of results. Kenyon and colleagues circumvent these issues by suppressing the insulin/IGF-1-like
daf-2
signaling pathway at specific stages in the life-span of
C. elegans
. The results of their investigation challenge our understanding of the evolution of aging and provide opportunities for future studies in mammalian models.
The Plot Thickens on Thin Bones
Authors: Davenport R. John
Published: August 2003

With age, bones thin and weaken, leaving the elderly susceptible to fractures. The affliction, known as osteoporosis, strikes millions of people, especially postmenopausal women. Recent strides in understanding the signals that control whether bone grows or shrinks offer insight into the causes of osteoporosis and promise to lead investigators to a new class of treatments. In addition, research is illuminating links between bone loss and other health problems such as heart disease.
Error Catastrophe in Mutant Mitochondria
Authors: Hoopes Laura L. Mays
Published: August 2003

The error catastrophe theory of aging, proposed by Orgel in 1963, predicted a decrease in the fidelity of information transfer that accelerated as aging progressed, until properly functioning macromolecules could no longer be reliably made. The theory was extensively tested by comparing DNA polymerases, transfer RNAs, and proteins derived from aging versus young animals, but it did not prove to have general applicability to the process of aging. Recently, the heritable eye disorder progressive external ophthalmoplegia has been found to result from mutation of the gene encoding DNA polymerase gamma, which replicates mitochondrial DNA. The mutant form of the polymerase replicates DNA less accurately than the wild-type enzyme, providing an explanation for the accumulation of mutations in the mitochondrial DNA of patients with this disorder. The affected mitochondria appear to exhibit an age-dependent error catastrophe. It is possible that other genetic diseases might result in error catastrophes in mitochondria as well.
Perennially Young?
Authors: Morgan Kendall
Published: August 2003

Compared with animals, plants seem to defy age. Many trees thrive for thousands of years--or maybe more. Some scientists attribute plants' knack for staying fresh to their segmented body plan and ability to renew spent parts. Yet emerging evidence suggests that plants can't elude feebleness entirely. They apparently suffer from the same wear and tear that animals do, an observation that calls their ultimate resilience into question.
Spotlight on Nematode Mitochondria in RNAi Mega-Screen
Authors: Melov Simon
Published: August 2003

An article in the current Advance Online Publication section of
Nature Genetics
reports the results of a large-scale RNA interference (RNAi) screen for genes that, when down-regulated, produce enhanced longevity in the nematode
Caenorhabditis elegans
. The down-regulation of a large number of genes related to energy metabolism and mitochondrial function yielded animals with increased life-spans, albeit with some additional deleterious phenotypes in some cases. In this Perspective, I discuss the implications of these results and make a plea for a more integrated approach in assessing the role of mitochondrial function, single gene mutations, and longevity.
Biologists Finally Horn In on Senescence in the Wild
Authors: Spencer Christine C. , Promislow Daniel E. L.
Published: August 2003

In 1995, biologists discovered an unusual new species, the antler fly (
Protophila litigata
). Antler flies inhabit discarded moose and deer antlers for most of their life cycle, and male antler flies exhibit sexually selected behaviors on their home antlers. It now turns out that these curious flies might provide new insights into the evolution of aging. For years, biologists assumed that senescence did not occur in the wild. But over the past decade, several studies of natural populations of birds and mammals have found age-related declines in rates of reproduction or survival, indicating senescence. A new study of antler flies by Bonduriansky and Brassil provides the first evidence for senescence in a wild invertebrate. The researchers are able to mark individual flies and follow them throughout their entire, albeit short, life-spans. This small species offers huge opportunities to study senescence and age-related selection on fitness characters in the wild.
Ageless Activist
Authors: Chen Ingfei
Published: August 2003

Neuroendocrinologist Paola Timiras believes it is a social duty of the university to teach about all phases of life, so she's embarking on a radical mission to create an undergraduate major in gerontology. The phases of her own life have included fleeing her native Italy with her family during World War II, breaking barriers as one of a handful of women in medical school, moving to Canada to escape communism, and crafting a celebrated career in academic research.
Europe Wakes Up to Aging
Authors: Weiss Giselle
Published: August 2003

With 20% of its residents currently aged 60 and up, Europe is outpacing the rest of the world in an elderly population boom. But it has neglected investigations into basic mechanisms of aging; these studies have historically received less funding than those on diseases of old age. Although the picture varies from nation to nation, research into the fundamental process of aging has gained priority status since the European Union's birth--but not enough, according to researchers in the field. A new E.U. program, kicked off last month, will back bigger science projects with larger piles of money, but the budget for aging-related research is still uncertain. The scarcity of money for studies on the fundamentals of aging stems largely from a lack of political interest in the subject.
Domino Effect
Authors: Seydel Caroline
Published: August 2003

Multiple DNA-wrapping proteins might execute calorie restriction's life-extending effects in fruit flies (Chromatin structure; Gene regulation; Calorie restriction).
One for All
Authors: Davenport R. John
Published: August 2003

A genetic manipulation that extends the lives of nematodes and fruit flies also delays death in mice, according to a new study. Previous research hinted that similar antiaging mechanisms function in mammals and their spineless cronies, but this result provides the clearest indication yet that the same longevity pathway operates in three diverse species. The finding confirms that information about aging gleaned from worms and flies applies to rodents and brings the knowledge one step closer to people.
Long Life Starts Early
Authors: Ramsayer Kate
Published: August 2003

Worms gain time by cutting energy production as larvae (Metabolism; Insulin-related signaling; Mitochondria; Genetics).
Molecular Immortality
Authors: Beckman Mary
Published: August 2003

Famous chromosome-protecting protein helps maintain master copy of DNA in stem cells (Stem cells; Cancer).
Age Discrimination
Authors: Leslie Mitch
Published: August 2003

A new study of knockout mice shows that neurons degenerate with age unless properly maintained. The findings emphasize the importance of upkeep for long-term functioning of neurons and clarify the role of an enigmatic gene. The results also might help researchers nail down what triggers some unexplained types of nerve degeneration in the elderly.
Rookie Rising
Authors: Chen Ingfei
Published: August 2003

Biologist Matt Kaeberlein has never quite managed to blend into the ranks. He was first to graduate in his class at the Massachusetts Institute of Technology, completing his Ph.D. in a mere 4 years and 3 months. During that time, he helped pinpoint the central gene that controls aging in brewer's yeast. Now, at the age of 31, he is vice president, as well as a co-founder, of biotech start-up Longenity.
Random Acts
Authors: Davenport R. John
Published: August 2003

Why senescence hits some cells earlier than others (Telomeres; Senescence).
The Burden of Pain on the Shoulders of Aging
Authors: Beckman Mary
Published: August 2003

More than 9% of the world population is older than 60. With age comes additional vulnerability to pain and the accumulation of insults that can engender ongoing misery. Insights into molecular and cellular aspects of pain might help escort people more comfortably into the senior ranks, but research that specifically addresses pain in the elderly is only now gearing up. Although a comprehensive understanding of how aging affects pain--and vice versa--is far off, experts report a good outlook for helping the millions of undertreated older people who experience pain on a daily basis.
Wake Up and Smell the Maillard Reaction
Authors: Monnier Vincent M. , Obrenovich Mark E.
Published: August 2003

The chemical reactions that occur when foods are browned during processing at high temperature also occur in the body during the natural aging process. Such reactions proceed at an accelerated rate in certain pathologies, such as diabetes, renal disease, atherosclerosis, and neurodegenerative diseases. A study now reveals that the consumption of foods rich in browned and oxidized products (so-called glycotoxins) induces a chronic inflammatory state in diabetic individuals. The study reveals a novel aspect at the interface between nutrition and disease, which might be especially relevant for the elderly and those with impaired renal function.
Osteoporosis Images
Authors: Mosekilde Lis
Published: August 2003

View more than a dozen images of bone from both young and old human subjects that illustrate age-related bone loss. The photos depict the deterioration of the so-called trabecular network--a spongy scaffold that lends strength to bone--of vertebrae that occurs with age and also show sites of bone resorption.

[View Images]
Losing Balance
Authors: Beckman Mary
Published: August 2003

Old bonemakers stimulate destructive forces in the skeleton (Osteoporosis).
Seedy Weed
Authors: Beckman Mary
Published: August 2003

Extra longevity gene might boost plant fecundity (Silencing; Chromatin).
An Engineer's Approach to the Development of Real Anti-Aging Medicine
Authors: de Grey Aubrey D. N. J.
Published: August 2003

In this Viewpoint, I list the various age-related molecular and cellular changes that are thought to limit mammalian life-span, and I outline a problem-solving approach to reversing these detrimental changes. This approach should help to prevent the development of these age-related changes into life-threatening pathologies and possibly, in due course, allow a large increase in healthy human life expectancy.
Shooting for the Stars
Authors: Chen Ingfei
Published: August 2003

As the first scientist in her family, biochemistry graduate student Bridget Williams tells fellow minority students, "If I can do it, you can do it." The initial experiments for her dissertation project didn't produce results, leading her to question whether science really was for her. But she kept at it, eventually finding a line of research that one of her mentors says will make an important contribution.
Death Be Not Degrading
Authors: Davenport R. John
Published: August 2003

Parkinson's protein trashes cell-suicide protein to block neuron death (Parkinson's disease; Protein degradation; Apoptosis).
Decorated for Death
Authors: Leslie Mitch
Published: August 2003

Tagging DNA-silencing protein trims survival in high-living yeast (Silencing).
γ-Secretase--Intramembrane Protease with a Complex
Authors: Wolfe Michael S.
Published: August 2003

γ-Secretase catalyzes intramembrane proteolysis of the amyloid β protein precursor, a process closely linked to the development of Alzheimer's disease. This protease also cleaves the transmembrane domain of the Notch receptor as part of a signaling pathway that is essential for proper embryonic develoment. Recent findings suggest that γ-secretase is a complex of at least four integral membrane proteins: presenilin, nicastrin, Aph-1, and Pen-2. Assembly of these four components apparently leads to autocleavage of presenilin into two subunits that together compose the intramembranous active site of γ-secretase. Understanding the mechanism of this unusual enzyme is important, as it is both a key therapeutic target and a founding member of a newly discovered class of intramembrane-cleaving proteases.
Mindful of Metal
Authors: Leslie Mitch
Published: August 2003

Harvard Medical School neuroscientist Ashley Bush likes to test his mettle, both in playing Australian-rules football and in promoting his theory that large amounts of metals set off the devastating neural damage of Alzheimer's disease. Corrupting β amyloid, the protein that jams the brains of AD patients, spurs production of harmful oxidants, he argues. Now, after more than a decade of effort, his work is beginning to win medals.
All That Jazz
Authors: Chen Ingfei
Published: August 2003

For Adam Antebi, a molecular biologist who has moonlighted as a professional saxophonist, science and music are as inextricably intertwined as the two strands of DNA's double helix. A conversation with him can drift from the cellular growth patterns of the slithering roundworm,
Caenorhabditis elegans
, to the legacies of jazz greats John Coltrane and Miles Davis, and he himself has crossed back and forth between the two worlds. He is currently a research group leader at the Max Planck Institute for Molecular Genetics in Berlin, where he has been unearthing insights into the genetics of development and aging in
C. elegans
. He has also jammed with the best in major jazz clubs, played backup for Aretha Franklin, and recorded with the popular ska band Bim Skala Bim and with jazz legends including Cyrus Chestnut, Marshall Allen, and Victor Gaskins.
Is DNA Cut Out for a Long Life?
Authors: Sinclair David
Published: August 2003

Much attention has been focused on the DNA repair hypothesis of aging. Studies in mammals that seek to test the validity of this model are complicated by both the functional redundancy and the essential nature of genes involved in the repair process. Compared to mammals, the study of DNA repair and aging in yeast has considerably fewer complicating factors. In this Perspective, I discuss results presented in this month's issue of
Aging Cell
that address whether the types of DNA damage repaired by the base excision repair pathway cause aging in yeast.
The Accidental Biologist
Authors: Chen Ingfei
Published: August 2003

Eugenia Wang's career represents a string of dogged, hard-earned achievements in transcending differences in gender, ethnicity, language, and culture. An authority on the study of programmed cell death and aging, Wang is a cell biologist at the University of Louisville School of Medicine in Kentucky, where she is starting up the future Gheens Center for Aging and Age-Related Diseases. She co-organized the Gordon Research Conference on the biology of aging in March 2003 and has coordinated National Institute on Aging-sponsored workshops on senescence. Her colleagues say she's earned a reputation as a hard-driving scientist with high standards, yet she's warm and caring as well. One can't help wondering how Wang does it all--have a family, run a lab, and handle all her administrative tasks. Her secrets include a supportive spouse, a can-do attitude, and people-managing skills that she gleaned from reading the biographies of military leaders.
Defects in Dynein Linked to Motor Neuron Degeneration in Mice
Authors: Andersen Julie
Published: August 2003

Although the causative genetic mutations for a subset of some of the most prevalent human motor neurodegenerative diseases have been identified, the exact molecular mechanisms behind motor neuron and associated muscular loss in these disorders remain an unsolved mystery. In a recent issue of
Science
, two mutagenesis-derived mouse mutants are described that contain missense mutations in the gene encoding the cytoplasmic dynein heavy-chain protein, which is part of a major cellular motor complex involved in retrograde axonal transport. These mutations result in progressive motor neuron degeneration in heterozygous animals and Lewy-like inclusion bodies in the homozygotes resembling those that occur in related human pathologies such as amyotrophic lateral sclerosis, spinal muscular atrophy, and spinal-bulbar muscular atrophy. This discovery opens up the exciting possibility that similar mutations may be involved in these human disease states.
Hungering for Simplicity
Authors: Strauss Evelyn
Published: August 2003

New work on yeast indicates that glucose restriction goads a protein without previously known antiaging talents to activate a longevity pathway. The protein, Pnc1p, acts through an enzyme called Sir2p that slows aging in several organisms, and the new results suggest an unexpected means of controlling Sir2p: with the small molecule nicotinamide. The work also supports the notions that glucose restriction activates a stress-response longevity pathway and that hormesis can counteract aging.
The Networker
Authors: Chen Ingfei
Published: August 2003

Molecular biologist Brian Clark is one of a cadre of European scientists who've been fostering international research collaborations on the biology of aging. Director of the Danish Centre for Molecular Gerontology at the University of Aarhus, he wears many hats as a scientist and an administrator in Denmark and beyond. Clark launched his career in the 1960s with groundbreaking work on protein synthesis at the Medical Research Council in Cambridge, U.K., and later began using his connections in the worlds of biochemistry and molecular biology to promote biogerontology research. In the '90s, he coordinated Molgeron and Genage, transnational initiatives funded by the European Commission to support conferences and exchanges of ideas among scientists who studied the molecular basis of aging. Outside of science, Clark holds a fascination for buses and professional soccer, and he has been known to call for timeouts in scientific discussions to go check on Liverpool's latest scores.
Telomerase and the Aging Heart
Authors: Heist E. Kevin , Huq Fawzia , Hajjar Roger
Published: August 2003

Telomeres are highly conserved structures that cap and protect the ends of linear chromosomes. The telomerase enzyme is present in germline cells as well as in many rapidly dividing tissues and serves to maintain chromosome length and integrity during cell division. Telomerase activity is typically reduced as an organism ages, and this phenomenon has been implicated in the aging process. In this Perspective, we focus on the effects of both gene knockout and gene replacement of telomerase in the heart and discuss the implications of these findings for potential cardiovascular therapeutics.
Overturned Ends
Authors: Beckman Mary
Published: August 2003

Ribosomes trump telomeres in premature-aging disease (Dyskeratosis congenita; Telomeres).
Great Expectations
Authors: Chen Ingfei
Published: August 2003

German-born grad student Florian Muller, 24, acquired the conviction while he was young that science can unravel the mysteries of the aging process. The precocious Muller channeled his energy into science in his teenage years, when he pondered the genetics of longevity and played with a home chemistry kit. In college at Washington State University in Pullman, he took graduate-level biology courses, did research in various labs, and published his first paper, about the free radical theory of aging, in his fifth year. Now in his first year of Ph.D. work at the University of Texas Health Science Center in San Antonio, he is busy at the bench and bursting with ideas for studying the role of oxidative damage in the aging process and in age-related diseases.
Creating New Neurons in Old Brains
Authors: Wise Phyllis M.
Published: August 2003

The brains of aged rodents exhibit decreased neurogenesis as compared to those of young adult rodents. Basal neurogenesis has previously been shown to increase in the young adult rodent brain upon the administration of growth factors. However, it is unknown whether similar treatment can affect this process in the aging brain. A recent paper published in the June 2003 issue of the journal
Aging Cell
reveals that two growth factors can stimulate neurogensis in aged mice. This result raises the possibility that similar treatments may be used in humans to help maintain normal brain function in old age.
Monitoring Proteins in Intact Cells
Authors: Berezovska Oksana , Bacskai Brian J. , Hyman Bradley T.
Published: August 2003

In the past decade, tremendous progress has been made in understanding the molecular mechanisms that underlie many neurodegenerative disorders, and common aspects of the pathological processes that lead to neuronal cell death have emerged. Nearly all of these advances have come from genetic, molecular, and biochemical studies that point to alterations in protein folding or protein-protein interactions as the fundamental mechanism behind these disorders. New microscopy/imaging technologies for detecting protein-protein interactions are now poised to contribute to progress in this field. Here we describe a novel technique based on fluorescence resonance energy transfer, called fluorescence lifetime imaging microscopy (FLIM), which allows monitoring of protein conformation and protein-protein interactions in intact cells. For example, using FLIM, we have studied the interaction of two proteins related to Alzheimer's disease: amyloid precursor protein (APP) and presenilin (PS-1). By measuring the lifetime of a donor fluorophore linked to PS-1, we show, with high subcellular resolution, localization of the PS-1-APP interaction within neurons. This approach may have widespread applicability in studies of neurodegenerative disease mechanisms.
Renaissance Woman
Authors: Chen Ingfei
Published: August 2003

In 2001, American developmental biologist Nadia Rosenthal embarked on an adventure: She moved abroad to head the European Molecular Biology Laboratory's mouse research campus in Monterotondo, Italy. The center studies the rodent to understand human diseases and uncover, among other things, strategies for regenerative medicine. As a child, Rosenthal had a passion for art; but after noticing nature's recurring designs in shells, plants, and animals, she decided to study the biology of pattern formation. Her research focuses on the genetics of skeletal muscle and heart development, and on muscle aging and regeneration. In her spare time, she creates artwork with scientific themes.
Urine-Concentrating Ability in the Aging Kidney
Authors: Sands Jeff M.
Published: August 2003

Urine-concentrating ability is decreased in the aging mammalian kidney. Studies have revealed various changes in kidney function that occur with aging and may explain the reduced ability to concentrate urine. Recently, the genes encoding many of the water- and solute-transport proteins and the vasopressin receptor, all of which are involved in urine concentration, have been cloned. Therefore, the molecular mechanisms that cause the reduction in urine-concentrating ability with aging can now be deciphered. In this Perspective, I discuss recent experiments designed to characterize this change in kidney function in aging mammals.
Does Anti-Aging Equal Anti-Microbial?
Authors: Lithgow Gordon J.
Published: August 2003

Aging is the dominant risk factor for human disease in developed countries. Could it be that a wide variety of disease states all have their origins in a common mechanism? Major signaling pathways that determine the rate of aging, such as the insulin/insulin-like growth factor 1 (IGF-1) pathway, might give clues to the nature of this major disease risk factor. It has now been shown that insulin/IGF-1 signaling influences
Caenorhabditis elegans
resistance to bacteria in such a way that long-lived worms are stress-resistant and slow to succumb to infection. Perhaps enhanced innate immunity is a feature of genetically determined longevity.
Science on the Fly
Authors: Chen Ingfei
Published: August 2003

As an ecologist, demographer, evolutionary biologist, and experimental geneticist all rolled into one, Marc Tatar cuts a wide swath in his studies linking reproduction, mortality, and longevity. He began his scientific training as a butterfly-chasing field biologist in the 1980s and, for a time, taught science in high school. Since then he has metamorphosed into a leader in investigating how insulin-like hormones influence aging in fruit flies. Using the tools of demography, he has studied senescence in fruit flies, seed beetles, and wild populations of grasshoppers, lions, and baboons. For fun, Tatar used to race bicycles and today swims 10 miles a week.
The Future of Human Longevity--How Important Are Markets and Innovation?
Authors: Vaupel James W.
Published: August 2003

In a hearing before the United States Senate Special Committee on Aging, a well-respected demographer warns that there is no evidence of slowing in the long-term rise in best-practice life expectancy in developed countries. The author discusses how these findings will affect the future of Social Security and argues for a larger, more focused effort with respect to longevity research by demographers, epidemiologists, and economists.