Sci. Aging Knowl. Environ., 23 February 2005
Vol. 2005, Issue 8, p. pe5
[DOI: 10.1126/sageke.2005.8.pe5]


Meeting Report: 4th European Congress of Biogerontology

Douglas A. Gray, and Alexander Bürkle

Douglas A. Gray is at the Ottawa Health Research Institute, 501 Smyth Road, Ottawa K1H 8L6, Canada. Alexander Bürkle is in the Department of Biology, University of Konstanz, D-78457 Konstanz, Germany. E-mail: dgray{at} (D.A.G.)

Key Words: biogerontology • gerontology • aging


In November 2004, the Assembly Rooms--a Georgian-era edifice constructed in Newcastle upon Tyne (Fig. 1) to host the "polite arts"--was the site of the 4th European Congress of Biogerontology. In a room where prior audiences were drawn to hear Strauss perform or to see Dickens direct his amateur theatre company, a gathering of biogerontologists convened, drawn by the promising program drafted by meeting organizer Thomas Kirkwood and his scientific committee. Over 4 days, this congregation was treated to novel insights from leading figures in the biology of aging. What follows are some highlights, with apologies to those speakers whose talks have been omitted due to the usual constraints.

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Fig. 1. A view of four of the landmark bridges in Newcastle upon Tyne, including the Swing Bridge (foreground), Queen Elizabeth II Bridge (immediately above), High Level Bridge (center), and the Tyne Bridge (at top). Bridges have occupied this site since a Roman structure spanned the river; the Swing Bridge was built over its pilings.

The tone of the Congress was set by a riveting keynote address from Linda Partridge (University College London) entitled "Diet, Death, and Demography." Partridge described well-characterized mutants of Drosophila, in which perturbation of the insulin/insulin-like growth factor signaling pathway has resulted in extended life span. In considering the mortality curves, she noted that increased life span could be accompanied by a change in slope (a lower rate of aging, as has been observed when flies are kept at lower temperatures) or a downward shift in the curve (which occurs in insulin-signaling mutants). Dietary restriction (see Masoro Subfield History and Kristal Perspective), a proven life-extending regimen that can easily be implemented in flies by diluting their food, shifts the curve but does not alter its slope (see "The Road More Traveled"). Partridge was interested in whether such a shift is the result of a decreased accumulation of age-related damage or greater tolerance to damage through some sort of increased vigor. To address this question, her laboratory switched the dietary regime very late in the game, and what they observed was a drop in the curve so that it was superimposed on the mortality curve of chronically restricted flies (see "Second Chance"). In flies it would therefore appear that dietary restriction works by increasing the capacity to tolerate accumulated damage. The mechanism of this increased vigor is currently unknown but of obvious import.

Session 1: Immune System Aging

The first thematic session of the Congress focused on changes in the immune system that occur with age (see "Immune Challenge" and Wollscheid-Lengeling Perspective). Infectious diseases are more frequent and more severe in the elderly, but Graham Pawelec (University of Tübingen) noted that unlike other diseases, they show no plateau at extreme old age (see "Losing Their Grip" and "Battle Scars"). He reviewed the evidence for the depletion of naïve T cells and their replacement with a population of anergic (nonresponsive) T cells already specific for herpesvirus epitopes; within a pool of T cells of fixed size, the increased proportion of herpes-specific clones would result in reduced ability to respond to other infections. He speculated on novel interventions by which T cell function might be improved in the elderly, listing telomerase-based therapies, proteasome reconstitution, and the use of antioxidants as possibilities. Because over a lifetime many of the body's T cells end up targeted against just a few chronic invaders such as cytomegalovirus (thus limiting the body's ability to fight new infection), antiviral therapy could also contribute to improved immunological health in later life.

The dysregulation of innate immunity may lead to poor response to infection or to chronic inflammation, depending on the balance of pro- and anti-inflammatory cytokine production by aging immune cells (see "Aging Takes Its Toll"). Anita van den Biggelaar (University of Leiden) presented recent data from the Leiden 85+ study, a survey of elderly individuals in the Netherlands who had reached or exceeded 85 years of age. She measured the production of cytokines from cultured peripheral blood lymphocytes stimulated by a bacterial toxin and correlated the cellular response figures with mortality data for the 85+ participants. Interestingly, van den Bigglelaar found that low production of pro- and anti-inflammatory cytokines was predictive of poor survival in old age.

The role of B cells in the decline of the immune system was the subject of a talk by Deborah Dunn-Walters (King's College London). She showed that the rate of immunoglobulin gene hypermutation in microdissected germinal centers did not change with age, but that the type of mutations and subsequent selection for B cells with "winning" Ig sequences operated differently in the gut versus the spleen. There was also evidence of reduced diversity in B cells, a finding that paralleled what the audience had heard previously with regard to T cells. Thus, it appears that the age-related decline of the immune system involves multiple cell populations.

Session 2: Protein Turnover in Aging

The role of protein turnover in aging was introduced by Bertrand Friguet (University of Paris), who listed the age-related modifications that generate damaged proteins and outlined the cellular mechanisms charged with the elimination of these potentially toxic entities. Friguet and Efstathios Gonos (National Hellenic Research Foundation) have studied the central importance of a macromolecular machine called the proteasome in the elimination of damaged proteins in the nucleus and cytosol, and of proteins extracted by retrograde transport from the endoplasmic reticulum. There is accumulating evidence from these investigators and others that proteasome function declines with age (see Gray Review), and Gonos has observed reduced proteasome activity in late-passage WI-38 fibroblasts, with a concomitant increase in oxidized and ubiquitinated proteins. He reported that as WI-38 cells approach senescence, they have reduced levels of {beta} proteasome subunits, whereas {alpha} subunit levels remain constant. Intriguing evidence was presented suggesting that overexpression of {beta}1 and {beta}5 subunits could coordinately induce proteasome subunit expression and increase proteasomal activity. The Gonos laboratory is exploring the potential therapeutic application of this approach. Douglas Gray, from the Ottawa Health Research Institute and a coauthor of this Perspective, has been studying transgenic mice expressing mutant isoforms of ubiquitin (the molecular tag for proteasomal targeting, among other cellular functions). Contrary to initial expectations, these mice have proved resistant to a variety of stressors. In addition, Gray presented evidence that some of his mutant lines also display signs of retarded aging, as evidenced by reduced accumulation of lipofuscin in the central nervous system, heart, and liver at 18 months of age. These data are in agreement with previously published work showing delayed aging in the testes of the transgenic mice. An interesting presentation by Isabelle Petropoulos (University of Paris) reminded the audience that oxidative damage to protein can in some cases be repaired, and the cell has enzymes dedicated to this function (see "The Two Faces of Oxygen"). Methionine oxidation can be reversed by the enzyme methionine sulfoxide reductase (Msr), and Petropoulos reported that the expression and activity of a subset of the Msr components decreased with aging. Experiments were described in which overexpression of MsrA protected WI-38 cells against oxidative stress (see "Auxiliary Rustproofing"). The session ended with a talk by Debbie Bevitt from the laboratory of Norman McKie (University of Newcastle upon Tyne). Bevitt and McKie are interested in the possible role of ADAMTS (a disintegrin A metalloproteinase with thrombospondin-type repeats) in age-related macular degeneration. Bevitt reported that the 5' untranslated region of ADAMTS6 mRNA is unusually long and contains 11 AUG codons upstream of what is believed to be the authentic start codon. Other ADAMTS mRNAs may be similarly endowed with upstream AUGs. It was hypothesized that there may be translational regulation of this family of proteinases, thought to be involved in the remodeling of the extracellular matrix, perhaps including the Bruchs membrane, which is of relevance to macular degeneration.

Session 3: Mitochondrial Functions in Aging

The mitochondrial theory of aging posits that the accumulation of somatic mitochondrial DNA (mtDNA) mutations should lead to a progressive decline in bioenergy associated with an increased production of reactive oxygen species (ROS) by mitochondria (see Nicholls Perspective). This could be viewed as a vicious cycle, because increased ROS production should lead to further deterioration of mtDNA. Douglass Turnbull and Laura Greaves (University of Newcastle upon Tyne) presented data on mtDNA mutations in tissue stem cells. mtDNA is a multicopy molecule, and the term "heteroplasmy" denotes the presence of a mixture of mitochondrial genomes (wild-type and mutant versions) in the same cell. The level of heteroplasmy is known to dictate the severity of the clinical phenotype in familial diseases caused by inherited mitochondrial mutations such as myoclonic epilepsy and ragged red fiber disease. In postmitotic cells taken from normal individuals, the accumulation of mutated mitochondrial genomes with aging is well established. This can be monitored in situ by a histochemical method for the staining of cytochrome c oxidase (COX)-deficient cells. The method can identify heteroplasmic cells carrying a minimum of 60% mutated mitochondrial genomes. A recent study by the Turnbull lab on human colonic crypt cells revealed staining of whole crypts, or longitudinal segments thereof, for COX deficiency, strongly suggesting the presence of a significant level of mtDNA mutations in the stem cells from which such crypts/segments arise (see "Crypt-ic Message"). The incidence of COX deficiency increased exponentially with age. No deletions in mtDNA were found, but instead a range of 60 different point mutations. About 50% of all cells in colonic mucosa harbor mtDNA mutations.

Marina Jendrach (Bereiter-Hahn lab, Johann-Wolfgang-Goethe University, Frankfurt) reported on fusion and fission of mitochondria in cultured human umbilical vascular endothelial cells (HUVECs) that were in either the proliferative or postmitotic (senescent) state. The fusion/fission process results in the mixing of mitochondrial components, including mtDNA. Although mitochondria in young cells displayed fast movements and frequent fusion/fission events, they moved more slowly in old cells and fusions/fissions occurred less often. In addition, mitochondria in postmitotic cells appeared aggregated, mostly localized to the perinuclear region, and had a lower membrane potential. The Jendrach data suggest age-associated loss of mitochondrial function that would not be obvious from examination of static microscopic images. Interestingly, fusions/fissions were inhibited in young cells when they were treated with exogenous oxidant compounds.

Podospora anserina is a filamentous fungus that undergoes a senescence syndrome accompanied by dramatic mtDNA reorganization (see "Copper Stopper"). Christian Scheckhuber (Osiewacz lab, Johann-Wolfgang-Goethe University, Frankfurt) reported on a dynamin-related gene (PaDnm1) that the group has identified in this organism, which plays a role in mitochondrial fission. Fusion and fission of mitochondria are in dynamic equilibrium in young cells, but mitochondrial fragmentation is a typical feature of senescence in this model organism. Overexpression of PaDnm1 in transfected Podospora did not alter mean life span, but fungi in which the PaDnm1 gene had been disrupted demonstrated an increase in life span from 22 days to at least 90 days (the experiments are still in progress). Apparently, the disruption of PaDnm1 tips the balance over to increased mitochondrial fusion, resulting in the formation of a mitochondrial network. Scheckhuber hypothesizes that adenosine triphosphate synthesis may be sustained for a longer time by the mitochondrial network.

Session 4: Telomeres and Replicative Senescence

Petra Boukamp (German Cancer Research Center, Heidelberg) pointed out that skin aging may be a phenomenon of dermal rather than epidermal aging, once again highlighting the fact that skin actually consists of two separate tissues: the dermis and epidermis. Even in old human skin, the epidermis looks still normal and its barrier function is well preserved. However, dramatic changes occur in the dermis, including in the dermal fibroblasts. Although telomere shortening is a well-established feature of aging in human cultured cells, including skin keratinocytes and fibroblasts, Boukamp reported that telomere length in human skin keratinocytes in situ can be quite variable, but telomeres do not show a statistically significant age-dependent decline. This is in good agreement with the fact that there is no loss of telomerase expression in the epidermis of older people. In keratinocytes, the expression of telomerase cannot be considered a stem cell marker, because it is the transient amplifying cell compartment that is the most important source of telomerase in skin. Telomerase expression is rapidly down-regulated in keratinocytes under standard in vitro culture conditions but is regained in organotypic culture by a histone deacetylation-dependent silencing and activation mechanism of the TERT gene promoter.

Maarten Linskens (University of Groningen) investigated for how many rounds of cell division cultured telomerase-transfected ("telomerized") human foreskin fibroblasts would stay normal. Linskins studied eight cell clones that had reached over 100 population doublings (PDs) after telomerization. At a rather low PD level, normal p53 and p21 responses were maintained upon genotoxic treatment and radiation sensitivity was normal. At around PD 300, however, DNA-damage-induced cell cycle arrest tended to be lost. In addition, some cultures had become tetraploid and displayed constitutive up-regulation of p53 with complete loss of p21cip1 (cyclin-dependent kinase inhibitor 1A). This was accompanied by diminished sensitivity to radiation. p16 was expressed at early passage levels but down-regulated in late-passage cells. Clearly, telomerized human fibroblasts tend to lose their normal karyotype and cell cycle regulation upon prolonged growth in culture.

David Kipling (University of Wales College of Medicine, Cardiff) focused on Werner syndrome (WS) fibroblasts aging. These cells display the shortest reported replicative life span of any human progeroid syndrome. Interestingly, TERT-mediated immortalization does not rescue all of the phenotypic changes. Single-telomere length analysis with the STELA technique, which detects telomeres of any size with equal efficiency, revealed that WS fibroblasts have a normal rate of telomere erosion, contradicting popular belief (see Aviv Perspective and "A Twist in an Early End"). Kipling presented a computational model of telomere dynamics and senescence that was based on the hypothesis of sequential overgrowth of faster-growing cells in mass cultures of WS cells, which would mean that WS cells double more often than the PD level would indicate. The model predicted that a cell population with a normal rate of telomere erosion and a certain rate of additional telomere-independent senescence events would display a growth behavior similar to that observed in WS.

Thomas von Zglinicki (University of Newcastle upon Tyne) reported on the role of {gamma}H2AX phosphorylation in cellular senescence. DNA double-strand breaks are known to induce {gamma}H2AX phosphorylation, which in turn activates the p53 pathway, and nuclear {gamma}H2AX-positive foci are typical features of irradiated cells. But {gamma}H2AX foci are also often found in unirradiated senescent human (and mouse) fibroblasts, localizing to the ends of chromosomes. Such foci can persist for periods of time up to months. Knocking down the expression of relevant kinases using small interfering RNA leads to restoration of DNA synthesis. Having established {gamma}H2AX as a marker for senescence in vitro, Zglinicki asked whether it might also be a marker for senescence in vivo. So far, some organ specificity seems to exist: Although old mouse kidney tissue displays very few {gamma}H2AX-positive cells, prominent staining was found in atherosclerotic plaques of the carotid artery, mostly due to staining of macrophages and smooth muscle cells.

Session 5: DNA Damage and Checkpoints

The next session addressed the relevance of DNA damage and checkpoints in the aging process (see Sinclair Perspective). Pidder Jansen-Dürr (Institute of Biomedical Aging Research, Innsbruck) is working on the role of stress-induced damage and aging in the HUVEC model. Contrary to human fibroblasts, HUVEC cultures have a senescence phenotype (at about 60 PDs) that is characterized by massive cell death near the final PD. The cultures display floating cells, enlarged nuclei, senescence-associated {beta}-galactosidase staining, scarcity of cells in S phase, activation of caspase-3, and facilitated apoptosis induction by exogenous ceramide. Jansen-Dürr obtained clear evidence for a role for ROS in endothelial cell aging: ROS levels were up-regulated in senescent cells, and a few selected proteins appeared to be prime targets for oxidation as revealed protein carbonyls detected by "oxyblot" (see "The Two Faces of Oxygen"). Furthermore, mild oxidant stress led to the induction of premature senescence in HUVECs. The search for the endogenous sources of ROS in senescent HUVECs by microrespirometry revealed that NADPH oxidases, rather than mitochondria, are likely candidates. The NADPH oxidase p67 subunit was up-regulated in HUVEC senescence.

Alexander Bürkle from the University of Konstanz and a coauthor of this Perspective presented data on the role of poly(ADP-ribosyl)ation, a DNA-damage-induced posttranslational modification of nuclear proteins, in the maintenance of the genomic stability of cultured cells under genotoxic stress. Experiments on transgenic mice selectively expressing a dominant negative poly(ADP-ribose) polymerase-1 (PARP-1) version in basal skin keratinocytes yielded concordant results: Transgenic mouse skin proved to be hypersensitive to chemically induced tumor formation. These functional data are in line with the a positive correlation between cellular poly(ADP-ribosyl)ation capacity and the life span of mammalian species, which Bürkle's group had reported previously (see Beneke Review).

David Lydall (University of Newcastle upon Tyne) presented budding yeast mutants undergoing immortalization without telomerase or recombination. Although it was known that yeast can overcome replicative crisis induced by the absence of telomerase via recombination-driven mechanisms, a yeast mutant simultaneously deficient for telomerase and recombination is able to grow, provided that the exonuclease exo1 is lacking as well. Lydall proposed a mechanism wherein abnormal chromosomes arise by duplication events/palindrome formation.

Stefano Salvioli (University of Bologna) focused on the human TP53 gene polymorphism Arg72Pro, carriers of which have a substitution of proline for arginine at position 72 in the p53 protein. This substitution in the transactivation domain has a functional impact on p53 activity. Whereas the Arg72 version preferentially localizes to the cytoplasm and induces apoptosis, the Pro72 version displays mostly nuclear localization and has more profound cell cycle effects mediated by p21WAF1/cip1 (cyclin-dependent kinase inhibitor 1A). Cells with at least one copy of Pro72 ("Pro+ cells") are less prone to camptothecin (topoisomerase-I inhibitor)-induced apoptosis and show a reduced proliferative potential. Pro+ fibroblasts express a higher basal level of p21, which is due to increased promoter activity, possibly resulting from more efficient binding of Pro72p53 to the p21 gene promoter. Interestingly, the phenotypic differences between Arg72 and Pro72 alleles were more pronounced in centenarian-derived cells.

Session 6: Early Life Impacts on Aging Processes

Marc Tatar (Brown University) addressed the later-life effects of retarded growth at an early stage (effects he refers to as the "Peter Pan syndrome"). In an insightful cross-species talk, Tatar summarized the available data for dwarfism, concluding that although increased longevity is a recurrent feature of dwarf mutants in both flies and mice (see "Dieting Dwarves Live It Up"), dwarfism is not sufficient for the longevity effect. He proposed a model that expanded on Kirkwood's disposable soma theory and suggested that the deleterious effects of reproduction on somatic survival were mediated by inhibitory signaling events, probably involving the endocrine pathways disrupted in dwarf mutants. The ability of organisms to allocate replaceable and nonreplaceable resources (stored fat, for example) would influence egg manufacture and hence the likelihood of reproduction. The tradeoff between fecundity and somatic maintenance was further explored in our own species through a remarkable study presented by Hans Meij from the University of Leiden. By collecting mortality data for 25,000 members of the Bimoba tribe of sub-Saharan Ghana and analyzing the survival of children of wives living in communal polygamous households, his group obtained evidence for decreased survival of children with multiple siblings, despite the sharing of resources and habitation. The higher mortality was attributed to reduced allocation of maternal resources to early somatic maintenance, which may manifest later as impaired innate immunity.

Timothy Cowen (University College London) changed the focus of the session from the level of human populations down to that of individual rat neurons, posing the question of why certain neurons are more vulnerable to aging than others. By painstakingly dissecting superior cervical ganglia from nerve growth factor (NGF)-treated or control animals, Cowen was able to demonstrate a pro-survival effect of the growth factor that was sensitive to PI3 kinase or mitogen-activated protein kinase inhibitors. NGF did not increase the life span of neurons (only their survival), and it may be that the differential sensitivity of neuronal populations is set by the availability of neurotrophins during early postnatal maturation.

Session 7: Functional and Pathological Changes

Session 7 dealt with functional and pathological changes of aging, with particular attention to skeletal muscle (see Hepple Perspective). Lars Larsson (Uppsala University) spoke on the mechanistic basis of age- and gender-related changes in muscle contraction. Using sophisticated devices for the measurement of the contractile speed of single muscle fibers, Larsson's group documented a decrease in contraction speed with age. Consistent with this decrease was reduced actin filament trajectories on self-assembled myosin molecules of specific isoforms. The mechanisms behind deteriorating contractile function are currently under investigation, but mass spectrometric analysis has revealed age-related glycation of the myosin active site. Janet Smith (University of Birmingham) has studied early-onset muscle fiber atrophy in the DBA/2J mouse as a model of age-related muscle loss. Her data suggest that the atrophy in these mice is not due to stem cell depletion but rather to the conversion of muscle fibers to fat.

Session 8: Progeroid Syndromes

Progeroid syndromes, conditions characterized by the premature onset of age-related symptoms, were the focus of the next session. Vilhelm A. Bohr (National Institute on Aging, Baltimore) reported on the WRN protein, which is deficient in the segmental progeroid syndrome WS (see "Of Hyperaging and Methuselah Genes"). This protein is a member of the RecQ family of helicases and possesses additional endonuclease function. Bohr reported that the best substrates for helicase activity in vitro are triple-stranded DNA and G quartets. A large number of interacting proteins have been identified, including PARP-1, Ku proteins, DNA-PKcs, Rad51, Rad52, BLM (the helicase deficient in Bloom syndrome; see "A Jump-Start for Replication"), and TRF2. In addition, subcellular colocalization of WRN and BLM has been shown. WRN is thought to coordinate different repair pathways, such as double-strand break repair and long-patch base-excision repair. This is also consistent with the fact that WS cells are hypersensitive to the mutagen 4-nitroquinoline-N-oxide and have increased levels of endogenously formed 8-hydroxyguanine in DNA. Recently, the link between WRN and telomeres has been strengthened by the demonstration of the presence of WRN at telomeres, the stimulation of WRN (and BLM) function by TRF2, and the requirement of short telomeres for typical WS pathology to develop in WRN knockout mice.

Another rare and severe progeroid syndrome is Hutchinson-Gilford progeria, characterized by growth failure, developmental defects, and the onset of an aged phenotype during childhood. In most cases analyzed, mutations in the LMNA gene, encoding lamin A (a protein that structurally reinforces the membrane surrounding the cell nucleus), seem to be responsible (see "Lamin-tation"). Lamins are intermediate filaments, and Chris Hutchison (University of Durham) termed lamin A "a guardian of the soma." He pointed out that the nuclear lamina is not only a physical load-bearing structure but that lamin A is also as a tissue-specific transcriptional silencer and regulator of the function of the retinoblastoma protein (pRB) via interaction with the nucleoskeleton protein LAP2{alpha}. If lamin A is lacking, pRB is subject to proteasomal degradation, thus leading to activation of E2F (a transcription factor required for the expression of a set of genes expressed during the DNA synthetic phase of the cell cycle). During normal aging, denatured lamin A protein seems to accumulate in senescent cells. Hutchinson posited that lamin A, with three cysteine residues in its C-terminal domain, might function as an oxidative stress sensor. Ian Kill (Brunel University) is studying the phenotype of Hutchinson-Gilford progeria at the cellular level. He reported a great variability in the maximal PD level of cells from different Hutchinson-Gilford syndrome patients. In these cells, aging is characterized by a period of hyperproliferation, in line with the above-mentioned deregulation of pRB function, and results in a large increase in the rate of apoptosis. Analysis of growth dynamics showed that the loss of replicating cells is the most prominent feature. Kill showed that the frequency of nuclear abnormalities was increased in early passage levels and even more so at high passage levels. Genomic instability as manifested by chromosomal loss is another feature of these cells. Lamin A staining reveals a highly variable pattern of rim staining and speckles, with a culture age-dependent increase in abnormal staining. Mild mechanical stretching of cells leads to an increased number of abnormal nuclei.

Final Session: Genetics of Human Aging

Eline Slagboom (Leiden University Medical Centre) led off the final session with an update on use of the prospective Leiden 85+ study in combination with nonagenarian sibling pairs and their families to identify genes of relevance to human aging. Preliminary analysis by linkage and association in the sibling studies of the Dutch population did not provide evidence for the involvement of a candidate gene on chromosome 4 previously identified by Thomas Perls. The Leiden sibling groups will be followed and genome scanning data will be reanalyzed once the sample size is larger. Irene Maeve Rea (Queens University Belfast) followed with an analysis of the highly polymorphic KIR receptors on natural killer (NK) cells. NK cells use these receptors to monitor the presence of human leukocyte antigen (HLA) molecules on cell surfaces; cells lacking HLA are considered foreign (nonself) and are lysed. KIR receptors were assayed on the NK cells of Irish octogenarians and nonagenarians versus younger controls. No evidence was found for altered KIR profiles in the elderly cohort.

An unexpected finding relating to the human p66shc gene was presented by Stefano Salvioli from the laboratory of Claudio Franceschi (University of Bologna) [see Martin Perspective]. p66shc knockout mice are known to have a significantly increased life span, and one might expect low levels of p66shc in long-lived persons. Examination of p66shc RNA levels in human centenarian fibroblasts revealed higher RNA levels than in control fibroblasts, contrary to the prediction. At the protein level, the difference was approximately twofold. It is currently not clear how the difference arises, but the Franceschi group has eliminated promoter methylation differences as a possible mechanism. The session ended with a talk by Maurizio Cardelli (Italian National Research Center on Aging, Ancona), who has studied a microsatellite polymorphism in a region of the human genome with a strikingly high density of Alu elements. The microsatellite repeat occurs in the YTHDF2 gene, and short alleles correlate with greater longevity and with higher gene expression. The function of this gene is not well understood, but the presence of an RNA binding motif in the predicted protein suggests a possible role in splicing or RNA metabolism.

The Congress adjourned at noon on 10 November, leaving participants free to explore the many delights of the city. Newcastle is a very old city; in some places one can still encounter structures built by the Romans. Walking along the quayside, one could not help being struck by Newcastle's remarkable rejuvenation. It was fitting to depart a superb biogerontology conference with this conspicuous civic demonstration of the decoupling of aging and decline.

February 23, 2005 Citation: D. A. Gray, A. Bürkle, Meeting Report: 4th European Congress of Biogerontology. Sci. Aging Knowl. Environ. 2005 (8), pe5 (2005).

Science of Aging Knowledge Environment. ISSN 1539-6150