The Max Planck Institute for Biology of Ageing, founded in 2008, is one of over 80 independent, non-profit-making institutes set up under the umbrella of the Max Planck Society. The overall research aim is to obtain fundamental insights into the aging process and thus to pave the way towards healthier aging in humans. An international research team drawn from almost 30 nations is working to uncover underlying molecular, physiological and evolutionary mechanisms.Located on the campus of Cologne University Hospital, this MPI forms a substantial part of a regional Life Science Cluster of closely interlinked research organizations focusing on research into ageing and ageing-associated diseases. Regional partners include the MPI for Neurological Research and the Cluster of Excellence CECAD as well as the DZNE and caesar Research Center .Together with their regional, national and international partners, such as ERIBA, researchers at the MPI for Biology of Ageing are exploring how cells age throughout the course of their life, which genes are involved and to what extent environmental factors play a role. Underlying processes are being studied in so-called model organisms: The genes of the mouse Mus musculus, the fruit fly Drosophila melanogaster and the roundworm Caenorhabditis elegans are known and the life expectancy of these organisms is relatively short. This makes them particularly suitable for research into the ageing process. Further model organisms in the form of the fish Nothobranchius furzeri and the yeast Saccharomyces cerevisiae are in use.Since the beginning of the research work in 2008 Adam Antebi , Nils-Göran Larsson and Linda Partridge are jointly directing the institute.The foundation stone for the new research premises was laid in 2010 and the building was inaugurated in 2013.As one of the youngest institutes of the Max Planck Society, the MPI for Biology of Ageing is expanding further and should eventually have a staff of about 350. At least ten research groups are planned as well as a fourth department under the leadership of a further director. Wikipedia.
News Article | April 17, 2017
It may not be the most appetizing way to extend life, but researchers have shown for the first time that older fish live longer after they consumed microbes from the poo of younger fish. The findings were posted to the bioRxiv.org preprint server on 27 March1 by Dario Valenzano, a geneticist at the Max Planck Institute for Biology of Ageing in Cologne, Germany, and his colleagues. So-called ‘young blood’ experiments that join the circulatory systems of two rats — one young and the other old — have found that factors coursing through the veins of young rodents can improve the health and longevity of older animals. But the new first-of-its-kind study examined the effects of 'transplanting' gut microbiomes on longevity. “The paper is quite stunning. It’s very well done,” says Heinrich Jasper, a developmental biologist and geneticist at the Buck Institute for Research on Aging in Novato, California, who anticipates that scientists will test whether such microbiome transplants can extend lifespan in other animals. Life is fleeting for killifish, one of the shortest-lived vertebrates on Earth: the fish hits sexual maturity at three weeks old and dies within a few months. The turquoise killifish (Nothobranchius furzeri) that Valenzano and his colleagues studied in the lab inhabits ephemeral ponds that form during rainy seasons in Mozambique and Zimbabwe. Previous studies have hinted at a link between the microbiome and ageing in a range of animals. As they age, humans2 and mice3 tend to lose some of the diversity in their microbiomes, developing a more uniform community of gut microbes, with once-rare and pathogenic species rising to dominance in older individuals4. The same pattern holds true in killifish, whose gut microbiomes at a young age are nearly as diverse as those of mice and humans, says Valenzano. “You can really tell whether a fish is young or old based on its gut microbiota.” To test whether the changes in the microbiome had a role in ageing, Valenzano’s team ‘transplanted’ the gut microbes from 6-week-old killifish into middle-aged 9.5-week-old fish. They first treated the middle-aged fish with antibiotics to clear out their gut flora, then placed them in a sterile aquarium containing the gut contents of young fish for 12 hours. Killifish don’t usually eat faeces, Valenzano notes, but they would probe and bite at the gut contents to see whether it was food, ingesting microbes in the process. The transplanted microbes successfully recolonized the guts of the fish that received them, the team found. At 16 weeks of age, the gut microbiomes of middle-aged fish that received 'young microbes' still resembled those of 6-week-old fish. The young microbiome ‘transplant’ also had dramatic effects on the longevity of fish that got them: their median lifespans were 41% longer than fish exposed to microbes from middle-aged animals, and 37% longer than fish that received no treatment (antibiotics alone also lengthened lifespan, but to a lesser extent). And at 16 weeks — old age, by killifish standards — the individuals that received young gut microbes darted around their tanks more frequently than other elderly fish, with activity levels more like 6-week-old fish. By contrast, gut microbes from older fish had no effect on the lifespans of younger fish, Valenzano and his team report. Exactly how microbes influence lifespan is hazy, Valenzano says. One possibility is that immune systems wear out with age, allowing harmful microbes to out-compete more beneficial bacteria. A microbiome transplant might, then, reset a middle-aged fish’s microbiome. Components of a more youthful microbiome could also promote longevity by somehow influencing the functioning of the immune system itself, Valenzano adds. “The challenge with all of these experiments is going to be to dissect the mechanism,” says Jasper. “I expect it will be very complex.” His laboratory is attempting microbiome swaps in differently aged fruit flies to test the impact on lifespan. Robert Beiko, a bioinformatician who studies microbial communities at Dalhousie University in Halifax, Canada, hopes to get funding to see whether microbiome swaps influence ageing in mice, too. He also wonders whether an individual’s own microbiome, sampled and preserved early in life, can extend its lifespan when reintroduced later. In humans, faecal transplants can help to treat some recurring infections, but Valenzano says it is far too early to consider the procedure for life extension. “I wouldn’t go that far. This is really early evidence that this has a potential positive effect.”
Tessarz P.,Gurdon Institute |
Tessarz P.,Max Planck Institute for Biology of Ageing |
Kouzarides T.,Gurdon Institute
Nature Reviews Molecular Cell Biology | Year: 2014
Post-translational modifications of histones regulate all DNA-templated processes, including replication, transcription and repair. These modifications function as platforms for the recruitment of specific effector proteins, such as transcriptional regulators or chromatin remodellers. Recent data suggest that histone modifications also have a direct effect on nucleosomal architecture. Acetylation, methylation, phosphorylation and citrullination of the histone core may influence chromatin structure by affecting histone-histone and histone-DNA interactions, as well as the binding of histones to chaperones. © 2014 Macmillan Publishers Limited. All rights reserved.
Le H.Q.,Max Planck Institute for Biology of Ageing
Nature Cell Biology | Year: 2016
Tissue mechanics drive morphogenesis, but how forces are sensed and transmitted to control stem cell fate and self-organization remains unclear. We show that a mechanosensory complex of emerin (Emd), non-muscle myosin IIA (NMIIA) and actin controls gene silencing and chromatin compaction, thereby regulating lineage commitment. Force-driven enrichment of Emd at the outer nuclear membrane of epidermal stem cells leads to defective heterochromatin anchoring to the nuclear lamina and a switch from H3K9me2,3 to H3K27me3 occupancy at constitutive heterochromatin. Emd enrichment is accompanied by the recruitment of NMIIA to promote local actin polymerization that reduces nuclear actin levels, resulting in attenuation of transcription and subsequent accumulation of H3K27me3 at facultative heterochromatin. Perturbing this mechanosensory pathway by deleting NMIIA in mouse epidermis leads to attenuated H3K27me3-mediated silencing and precocious lineage commitment, abrogating morphogenesis. Our results reveal how mechanics integrate nuclear architecture and chromatin organization to control lineage commitment and tissue morphogenesis. © 2016 Nature Publishing Group
Rugarli E.I.,University of Cologne |
Langer T.,University of Cologne |
Langer T.,Max Planck Institute for Biology of Ageing
EMBO Journal | Year: 2012
Neuronal survival critically depends on the integrity and functionality of mitochondria. A hierarchical system of cellular surveillance mechanisms protects mitochondria against stress, monitors mitochondrial damage and ensures the selective removal of dysfunctional mitochondrial proteins or organelles. Mitochondrial proteases emerge as central regulators that coordinate different quality control (QC) pathways within an interconnected network of mechanisms. A failure of this system causes neuronal loss in a steadily increasing number of neurodegenerative disorders, which include Parkinson's disease, spinocerebellar ataxia, spastic paraplegia and peripheral neuropathies. Here, we will discuss the role of the mitochondrial QC network for neuronal survival and neurodegeneration. © 2012 European Molecular Biology Organization.
Gems D.,University College London |
Partridge L.,Max Planck Institute for Biology of Ageing
Annual Review of Physiology | Year: 2013
Discovering the biological basis of aging is one of the greatest remaining challenges for science. Work on the biology of aging has discovered a range of interventions and pathways that control aging rate. A picture is emerging of a signaling network that is sensitive to nutritional status and that controls growth, stress resistance, and aging. This network includes the insulin/IGF-1 and target of rapamycin (TOR) pathways and likely mediates the effects of dietary restriction on aging. Yet the biological processes upon which these pathways act to control life span remain unclear. A long-standing guiding assumption about aging is that it is caused by wear and tear, particularly damage at the molecular level. One view is that reactive oxygen species (ROS), including free radicals, generated as by-products of cellular metabolism, are a major contributor to this damage. Yet many recent tests of the oxidative damage theory have come up negative. Such tests have opened an exciting new phase in biogerontology in which fundamental assumptions about aging are being reexamined and revolutionary concepts are emerging. Among these concepts is the hyperfunction theory, which postulates that processes contributing to growth and reproduction run on in later life, leading to hypertrophic and hyperplastic pathologies. Here we reexamine central concepts about the nature of aging. Copyright © 2013 by Annual Reviews. All rights reserved.
Fontana L.,University of Washington |
Fontana L.,University of Brescia |
Partridge L.,Max Planck Institute for Biology of Ageing |
Partridge L.,University College London
Cell | Year: 2015
Reduced food intake, avoiding malnutrition, can ameliorate aging and aging-associated diseases in invertebrate model organisms, rodents, primates, and humans. Recent findings indicate that meal timing is crucial, with both intermittent fasting and adjusted diurnal rhythm of feeding improving health and function, in the absence of changes in overall intake. Lowered intake of particular nutrients rather than of overall calories is also key, with protein and specific amino acids playing prominent roles. Nutritional modulation of the microbiome can also be important, and there are long-term, including inter-generational, effects of diet. The metabolic, molecular, and cellular mechanisms that mediate both improvement in health during aging to diet and genetic variation in the response to diet are being identified. These new findings are opening the way to specific dietary and pharmacological interventions to recapture the full potential benefits of dietary restriction, which humans can find difficult to maintain voluntarily. © 2015 Elsevier Inc.
Larsson N.-G.,Max Planck Institute for Biology of Ageing
Annual Review of Biochemistry | Year: 2010
Mitochondrial dysfunction is heavily implicated in the multifactorial aging process. Aging humans have increased levels of somatic mtDNA mutations that tend to undergo clonal expansion to cause mosaic respiratory chain deficiency in various tissues, such as heart, brain, skeletal muscle, and gut. Genetic mouse models have shown that somatic mtDNA mutations and cell type-specific respiratory chain dysfunction can cause a variety of phenotypes associated with aging and age-related disease. There is thus strong observational and experimental evidence to implicate somatic mtDNA mutations and mosaic respiratory chain dysfunction in the mammalian aging process. The hypothesis that somatic mtDNA mutations are generated by oxidative damage has not been conclusively proven. Emerging data instead suggest that the inherent error rate of mitochondrial DNA (mtDNA) polymerase γ (Pol γ) may be responsible for the majority of somatic mtDNA mutations. The roles for mtDNA damage and replication errors in aging need to be further experimentally addressed. © 2010 by Annual Reviews. All rights reserved.
Tatsuta T.,University of Cologne |
Scharwey M.,University of Cologne |
Langer T.,University of Cologne |
Langer T.,Max Planck Institute for Biology of Ageing
Trends in Cell Biology | Year: 2014
Mitochondria are dynamic organelles surrounded by two membranes with a defined lipid composition. The majority of lipids are synthesized in the endoplasmic reticulum (ER) and transported to the mitochondria, but the synthesis of cardiolipin and phosphatidylethanolamine in the inner membrane of mitochondria highlights their general importance for cellular lipid metabolism. Extensive exchange of lipids and their precursors occurs between the ER and mitochondria as well as between mitochondrial membranes. The recent identification of membrane-tethering complexes and lipid-transfer proteins in mitochondria now provides the first insight into the mechanisms of these transport processes, which are of fundamental importance for mitochondrial activities and cell homeostasis. Here, we summarize the current understanding of lipid trafficking at the mitochondria and discuss emerging models for the mechanisms of lipid transfer. © 2013 Elsevier Ltd.
Stewart J.B.,Max Planck Institute for Biology of Ageing |
Chinnery P.F.,Northumbria University
Nature Reviews Genetics | Year: 2015
Common genetic variants of mitochondrial DNA (mtDNA) increase the risk of developing several of the major health issues facing the western world, including neurodegenerative diseases. In this Review, we consider how these mtDNA variants arose and how they spread from their origin on one single molecule in a single cell to be present at high levels throughout a specific organ and, ultimately, to contribute to the population risk of common age-related disorders. mtDNA persists in all aerobic eukaryotes, despite a high substitution rate, clonal propagation and little evidence of recombination. Recent studies have found that de novo mtDNA mutations are suppressed in the female germ line; despite this, mtDNA heteroplasmy is remarkably common. The demonstration of a mammalian mtDNA genetic bottleneck explains how new germline variants can increase to high levels within a generation, and the ultimate fixation of less-severe mutations that escape germline selection explains how they can contribute to the risk of late-onset disorders. © 2015 Macmillan Publishers Limited. All rights reserved.
Kukat C.,Max Planck Institute for Biology of Ageing |
Larsson N.-G.,Max Planck Institute for Biology of Ageing |
Larsson N.-G.,Karolinska Institutet
Trends in Cell Biology | Year: 2013
Mitochondria contain mtDNA derived from the ancestral endosymbiont genome. Important subunits of the oxidative phosphorylation system, which supplies cells with the energy currency ATP, are encoded by mtDNA. A naked mtDNA molecule is longer than a typical mitochondrion and is therefore compacted in vivo to form a nucleoprotein complex, denoted the mitochondrial nucleoid. Mitochondrial transcription factor A (TFAM) is the main factor packaging mtDNA into nucleoids and is also essential for mtDNA transcription initiation. The crystal structure of TFAM shows that it bends mtDNA in a sharp U-turn, which likely provides the structural basis for its dual functions. Super-resolution imaging studies have revealed that the nucleoid has an average diameter of ~100. nm and frequently contains a single copy of mtDNA. In this review the structure of the mitochondrial nucleoid and its possible regulatory roles in mtDNA expression will be discussed. © 2013 Elsevier Ltd.