Sci. Aging Knowl. Environ., 5 January 2005
Vol. 2005, Issue 1, p. pe1
[DOI: 10.1126/sageke.2005.1.pe1]

PERSPECTIVES

Report on the 14th Annual Meeting of the German Society for Geriatric Research

Christian Scheckhuber

The author is at the Department of Molecular and Developmental Biology and Biotechnology, Botanic Institute, J. W. Goethe University, Marie-Curie-Strasse 9, 60439 Frankfurt, Germany. E-mail: scheckhuber{at}em.uni-frankfurt.de

http://sageke.sciencemag.org/cgi/content/full/2005/1/pe1

Key Words: diapause • heart • microglial cells • mitochondria • neurogenesis • reactive oxygen species

The Deutsche Gesellschaft für Alternsforschung, or German Society for Geriatric Research, was founded in 1990 by German physicians and natural scientists. The main focus of the organization is the presentation and discussion of new results in gerontologic and geriatric science, and on 13 November 2004, the 14th annual meeting, organized by H. Frenzel, took place at the Pathology Institute in Karlsruhe. The meeting was divided into two sessions, covering, respectively, topics in molecular and cellular aging and in geriatrics. In this meeting report, I will describe selected talks from the first session of the meeting in detail.

An introductory talk about age-related macular degeneration (ARMD) was given by A. J. Augustin, director of the Ophthalmic Department at the Karlsruhe clinic. ARMD is an important cause of visual impairment in the developed world (see "The Eyes Have It"), the disease often occurring after the surgical removal of cataracts. Remodelling of Bruch's membrane, a layer of extracellular matrix that lies in the retina, is a critical feature of ARMD. Protection against phototoxic reactions is impaired in the aged eye, one reason for this being a lowered concentration of the pigment melanin, which dissipates photonic energy to heat. Artificial lenses are thus equipped with a blue light filter which protects the macula (the portion of the retina responsible for central vision). Augustin discussed the eye-protective properties of two carotenoid pigments, lutein and zeaxanthin. Several drugs that are used to treat ARMD, such as Macugen (Pfizer), Retaane (Alcon), and Lucentis (Novartis), were also presented.

C. Scheckhuber, from H. D. Osiewacz's laboratory at the Johann Wolfgang Goethe University in Frankfurt and the author of this Perspective, presented data on aging of the filamentous ascomycete Podospora anserina (see "Copper Stopper"). This fungus has been a model system for the study of aging for more than 50 years. Mitochondria play a key role in the aging process in this organism [for a review, see (1)]. A gene involved in mitochondrial fission in P. anserina was recently identified by suppressive subtractive hybridization (a method for isolating differentially expressed genes), using transcripts from a wild-type strain and the long-lived Podospora mutant grisea, and was named PaDnm1. PaDnm1 shows significant homology to genes encoding dynamin-related proteins that are involved in mitochondrial division in yeast, plants, nematodes, and mammals (2). Overexpression of this gene leads to increased mitochondrial fission but has no detectable effect on life span. Disruption of PaDnm1 leads to the formation of mitochondrial networks or extremely elongated mitochondria, whereas these organelles normally resemble short filaments in P. anserina. Initial experiments hint that loss of PaDnm1 function is correlated with a marked increase in life span; it may be that this is caused by a higher level of adenosine triphosphate synthesis than observed in the wild-type fungus.

K.-G. Collatz from the University of Freiburg described survival during diapause of the beetle Gastrophysa viridula. This insect is common in Europe, living on Rumex (a member of the buckwheat family) leaves, and during the cold winter months adult animals hibernate in a diapause state (similar to the dauer larva formed by nematode worms; see "Dauer Power"). The mortality rate of the beetles in diapause is constant over long periods of time, whereas diapause-free animals show a typical senescence curve, as mortality increases with time. In fact, beetles undergoing diapause live about four times longer than diapause-free animals, indicating that the process of aging is interrupted during the insects' hibernation. However, the metabolic basis of this phenomenon remains to be elucidated.

Porifera (sponges) were the model system used to study aging featured in the talk by H. C. Schröder from the University of Mainz. Mechanisms of differentiation and cellular senescence have been investigated in three-dimensional aggregates of cells, known as primmorphs. Do Porifera contain pluripotent stem cells? Genetic experiments indicate that Suberites domuncula has two genes whose counterparts have been reported to be expressed specifically in the stem cells of higher metazoa. The expression of one of these genes, called noggin, is induced in the presence of silicate and ferric ions in primmorphs. Schröder has demonstrated that Porifera also seem to possess apoptotic mechanisms, because characteristic caspase enzymes that are active in apoptosis, the pro-apoptotic DD2 and anti-apoptotic Bcl-2, could be identified in their model system (3, 4).

Moving into mammalian organisms, S. Otto and colleagues, from F. Keller's laboratory at the University of Leipzig, examined the elastic fibrous system of cardiac valves (which is functionally important because it has contractile properties) during human aging. It appears that atrial fibers are significantly more numerous than ventricular fibers. There is an increase in the number of elastic fibers up to the age of 50, but subsequently the fibrous system gets progressively weaker, which might account for the more severe consequences of heart dysfunction in elderly people.

C. Mozet from K. Welt's group (University of Leipzig) described the changes in mitochondrial morphology observed in heart muscle cells during aging in Wistar rats. Surprisingly, only moderate changes are seen in mitochondrial parameters such as organelle volume and the number of cristae. Protection against reactive oxygen species (ROS) (see "The Two Faces of Oxygen") seems to be higher in aged cells, as shown by elevated superoxide dismutase activity. In contrast, the tolerance of hypoxic stress is much lower in old heart muscle cells, as indicated by analyses performed using transmission electron microscopy. Under hypoxic stress, mitochondria displayed an increased volume, larger degenerated areas (the mitochondrial matrix showed a patchy morphology and the appearance of pronounced cavitations), and a reduced number of cristae. Feeding the rats with an extract of Ginkgo biloba (EGb 761) had a protective effect, and the aforementioned mitochondrial aberrations were significantly reduced. EGb 761 contains flavonoids and terpenes that probably act as free-radical scavengers.

T. Grune from the University of Düsseldorf spoke on the oxidation of proteins and aging in the brain. The proteasome is responsible for degrading oxidatively modified proteins but, during the process of aging, proteasome function is progressively impaired, so that damaged proteins accumulate within the cell (5) (see Gray Review). To gain new insights into the process, microglial cells were isolated from juvenile and senescent mice. Microglia are the smallest of glial cells: Some act as phagocytes to clean up central nervous system debris, whereas most serve as representatives of the immune system in the brain (see figure 2 in McGeer Perspective). When these protective cells age, their ability to release a burst of cytolytic ROS when treated with stimulants (elicitor molecules of bacterial or fungal origin) is reduced. If, however, alpha tocopherol (vitamin E) is added to senescent microglial cells, they regain the ability to respond to stimulation with an oxidative burst. A further important effect is the observed increase in proteolytic activity of the proteasome. This finding can be explained by the fact that alpha tocopherol suppresses expression of the gene encoding the microglial cell surface receptor CD36, which is needed for the uptake of apoptotic vesicles. These vesicles normally inhibit proteasome activity by the release of proteinaceous aggregates. The findings suggest that alpha tocopherol can prevent this process and partially reactivate microglia.

A. Popa-Wagner, from the Ernst Moritz Arndt University in Greifswald, presented new data on the transient appearance of proliferating cells in the aged rat brain after stroke. The age-related decline in the plasticity of the rodent brain may be associated with a decreased rate of neurogenesis (see Wise Perspective). Because aging is both a risk factor for stroke and an impediment to recovery, cellular events associated with neurogenesis after stroke in young and aged rats were studied by producing focal cerebral ischemia by reversible occlusion of the right middle cerebral artery in 3-month- and 20-month-old male Sprague-Dawley rats, and the functional outcome was studied at 3, 7, 14, and 28 days after surgery by means of a variety of neurological and behavioral tests. At each time point, brains were removed, sectioned, and immunostained for the microglial marker ED-I, the astrocytic marker glial fibrillary acidic protein (GFAP), the endothelial cell marker RECA, and the label for dividing cells bromodeoxyuridine (BrdU) (which is incorporated into newly synthesized DNA), as well as the stem cell marker nestin, and doublecortin, which is used for monitoring the migration of neurons. The results showed that infarct development in young rats was slow and could be explained by the phenomenon of delayed neuronal death: The vulnerability of brain tissue to cerebral ischemia increases with age. Apoptosis is not a major contributor to cell death in this model. An increase in cerebrovascular permeability at the blood-brain barrier was noted. A three-dimensional reconstruction of BrdU cells in the infarcted area of aged rat brains revealed that most of the BrdU cells either derived from the vasculature, stained with the endothelial cell marker RECA, or leaked in from the circulation. BrdU immunocytochemistry revealed numerous cells in the periventricular zone (part of the hypothalamus in the diencephalon, which contains the suprachiasmatic nucleus for the synchronization of circadian rhythms with light/dark cycles, control neurons for the autonomic nervous system, and secretory neurons) of both young and aged rats that appeared to be migrating from there to the corpus callosum, which is situated in the telencephalon and is essential for interhemispheric communication. Some of these cells colocalized at day 3 with nestin, a marker for immature neurons both in young and, significantly, also in aged rats. However, although neurogenesis persists in young rats, the number of BrdU cells colocalizing with nestin rapidly disappeared as a function of age. These results show that aged rats mount a neurogenic response to ischemic damage that is transient in nature, and most newly born neuroepithelial cells will become incorporated into blood vessels at the infarct border.

The meeting successfully combined many different aspects of the phenomenon of aging. Results yielded by fundamental research on model organisms such as P. anserina (fungus), Suberites domuncula (sponge), and G. viridula (beetle) offer exciting insights into the aging process in these systems. Several important questions remain to be answered: Why does the altered mitochondrial morphology lead to an apparent life span extension in P. anserina? Are there further components in the apoptotic machinery of sponges yet to be discovered, and how does this kind of cell death work in these organisms? What are the physiological mechanisms that decrease the mortality of G. viridula in diapause? Resolving these questions experimentally will doubtless be very worthwhile. However, interesting findings were also presented at the meeting concerning topics such as oxidative stress in the brain, the neurogenic response to stroke, and morphological cardiac alterations that can hopefully contribute to the development of better medical treatments for age-related human diseases.


January 5, 2005
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  2. G. Praefcke, H. T. McMahon, The dynamin superfamily: Universal membrane tubulation and fission molecules. Nat. Rev. Mol. Cell Biol. 5, 133-147 (2004).[CrossRef][Medline]
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  5. T. Grune, T. Jung, K. Merker, K. J. Davies, Decreased proteolysis caused by protein aggregates, inclusion bodies, plaques, lipofuscin, ceroid, and 'aggresomes' during oxidative stress, aging, and disease. Int. J. Biochem. Cell Biol. 36, 2519-2530 (2004).[CrossRef][Medline]
Citation: C. Scheckhuber, Report on the 14th Annual Meeting of the German Society for Geriatric Research. Sci. Aging Knowl. Environ. 2005 (1), pe1 (2005).








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