Gene expression signatures of human cell and tissue longevity

HFSP supports novel, innovative and interdisciplinary basic research focused on the complex mechanisms of living organisms. A clear emphasis is placed on novel collaborations that bring biologists together to focus on problems at the frontier of the life sciences. In this section you find information about the awardees in the HFSP scientific programs. The Human Frontier Science Program is a program of funding for frontier research in the life sciences. Synapses are specialized cell adhesions that are the fundamental functional units of the nervous system. However, the extracellular signals that induce synapse formation in the central nervous system CNS are poorly understood. By using highly purified populations of neurons and glia, the Barres Lab has shown that the number of synapses on retinal ganglion cells RGCs in culture is enhanced 7-fold by soluble signals released by astrocytes. Recently, the Barres Lab has identified thrombospondin TSP , a kD, astrocyte-secreted protein, as a protein that plays a crucial role in astrocyte-enhanced synaptogenesis. TSP is sufficient to induce structural synapses in vitro and is highly localized to synapses throughout the developing brain. The goal of this proposal is to understand the molecular and cellular mechanisms by which TSP promotes structural synapses in vitro and to determine whether TSP also regulates synaptogenesis in vivo.


All patents, patent applications, and references cited in this specification are hereby incorporated by reference, in their entireties. In some organs, cells undergo continuous turnover, and old cells are replaced by new ones. Often, mature or differentiated cells can divide to give rise to more cells of the same type. Yet, differentiated cell types such as neurons are unable to divide. In such cases, new cells are generated by less differentiated stem or progenitor cells.

We have measured 14C from nuclear bomb tests in genomic DNA of human myocardial cells, which allows retrospective birth dating ().

JavaScript is disabled for your browser. Some features of this site may not work without it. Impact of alcohol and drug abuse on hippocampal neurogenesis in humans Author: Dhanabalan, Gopalakrishnan. Date: Time: Abstract Hippocampus is one of the few brain regions in which adult neurogenesis is known to occur. Adult neurogenesis in the hippocampus is considered to be important for higher cognitive function, most notably in memory processes and mood regulation. Alcohol abusers are often diagnosed with memory dysfunction.

Several animal studies have reported impairment of alcohol on adult neurogenesis in hippocampus, however in studies of adult human alcohol abusers, no conclusive results have been obtained so far. The work presented in this thesis focuses on understanding the effect of alcohol on hippocampal neurogenesis and is based on studies of carefully phenotyped postmortem human subjects.

Further, hippocampal cell turnover was studied regarding the effect of alcohol and cocaine using retrospective bomb-pulse derived carbon birth dating procedure. All subjects included in this study had an on-going alcohol abuse for at least four weeks prior to death, a time period that was chosen based on data about the time that elapse from that a neural stem cell after asymmetric division becomes an integrated neuron in the granule cell layer of the dentate gyrus.

Does The Human Body Replace Itself Every Seven Years?

The immediate environmental effects of nuclear bomb testing during the Cold War era were undoubtedly devastating. Having left enormous negative environmental and socioeconomic impacts all over the world, it is hard to imagine that any sort of silver lining to these tests could exist. But despite all the destruction that these tests caused, their remnants are now being used to answer questions in biology that might otherwise have been unsolvable or, at the least, extremely difficult to study.

birth dating and population modeling to retrospectively infer the Measurement of human cell birth with stable isotope tracers and MIMS.

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Adult human neurogenesis: from microscopy to magnetic resonance imaging

Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue.

However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested.

Retrospective radiocarbon dating • Cardiomyocyte proliferation Figure 1 Retrospective radiocarbon (14C) birth dating of human cells in the.

Po0 , 05 women versus men. Wilcoxon rank-sum test for difference in medians. Youngren , Synchrony in telomere length of the human fetus , Human Genetics , vol. DOI : Kimura , Synchrony of telomere length among hematopoietic cells , Experimental Hematology , vol. Blackburn , Telomeres and telomerase: their mechanisms of action and the effects of altering their functions , FEBS Letters , vol. Yui, C.

Unexpected Lessons Learned from Mid-Century Atomic Bomb Explosions

C-dating in archeology is used for determining the age of the biological material. Similar to this method, it is possible to retrospectively determine the age of cells without the need for delivering any chemical to the individual. Extensive testing of nuclear weapons between the mid s and early s resulted in the generation of large quantities of 14 C, which rapidly distributed evenly in the atmosphere around the globe.

The generation of cells in the human body has been difficult to study, and our understanding of cell turnover is limited. Testing of nuclear weapons resulted in a​.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. A Nature Research Journal. Different cell types within the body exhibit substantial variation in the average time they live, ranging from days to the lifetime of the organism.

The underlying mechanisms governing the diverse lifespan of different cell types are not well understood. To examine gene expression strategies that support the lifespan of different cell types within the human body, we obtained publicly available RNA-seq data sets and interrogated transcriptomes of 21 somatic cell types and tissues with reported cellular turnover, a bona fide estimate of lifespan, ranging from 2 days monocytes to a lifetime neurons. Exceptionally long-lived neurons presented a gene expression profile of reduced protein metabolism, consistent with neuronal survival and similar to expression patterns induced by longevity interventions such as dietary restriction.

Across different cell lineages, we identified a gene expression signature of human cell and tissue turnover. In particular, turnover showed a negative correlation with the energetically costly cell cycle and factors supporting genome stability, concomitant risk factors for aging-associated pathologies.

Paxinos-Watson Award

This award has been made possible by a generous donation to the Society by Professor George Paxinos and Professor Charles Watson, commemorating the new edition of their important key reference text “The Rat Brain in Stereotaxic Coordinates” by Academic Press. The award was established for the most significant neuroscience paper published by any Member of the Society, and is judged annually. Only the first and senior authors will receive a certificate, and the prize money will be sent to the nominating author.

Plitzko, Wolfgang Baumeister, Laurence J. Miller, Deborah L.

Retrospective Birth Dating of Cells in Humans. Kirsty L. Spalding,1 Ratan D. Bhardwaj,1 room for controversy (Nowakowski and Hayes, ;.

Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI: Spalding and R. Bhardwaj and B. Buchholz and H. Druid and J. Spalding , R. The generation of cells in the human body has been difficult to study, and our understanding of cell turnover is limited. Testing of nuclear weapons resulted in a dramatic global increase in the levels of the isotope 14C in the atmosphere, followed by an exponential decrease after We show that the level of 14C in genomic DNA closely parallels atmospheric levels and can be used to establish the time point when the DNA was synthesized and cells were born.

View on Elsevier.

Dynamics of oligodendrocyte generation in multiple sclerosis

Adult neurogenesis appears very well conserved among mammals. It was, however, not until recently that quantitative data on the extent of this process became available in humans, largely because of methodological challenges to study this process in man. There is substantial hippocampal neurogenesis in adult humans, but humans appear unique among mammals in that there is no detectable olfactory bulb neurogenesis but continuous addition of new neurons in the striatum.

There has been an enormous expansion in the knowledge regarding adult neurogenesis in experimental animals over the last two decades.

Retrospective birth dating of cells in humans. Cell ; Pubmed. Huttner HB, Bergmann O, Salehpour M, Rácz A, Tatarishvili J.

Author s : Maggie S. To assess the dynamics of cell generation in multiple sclerosis, we retrospectively birth-dated mature oligodendrocytes from post-mortem human brain tissue. We took advantage of the markedly increased levels of atmospheric 14 C levels caused by nuclear bomb tests during the Cold War When a cell duplicates its chromosomes during mitosis, it will integrate 14 C in the genomic DNA at a concentration that corresponds to that in the atmosphere and create a stable date mark for when the cell was born.

Integration of 14 C in the human body can be measured with a precision of [plus or minus]1. By comparing the level of 14 C in genomic DNA to that in the atmosphere, it is possible to infer the age, and with mathematical modelling calculate the turnover dynamics of a cell population 5,10, We used a previously established strategy to isolate mature oligodendrocyte cell nuclei to high purity by flow cytometry from human post-mortem brain tissue using antibodies to SOX10, which is expressed at all maturational stages in the oligodendrocyte lineage, and the monoclonal antibody CC1, which specifically labels the cell nuclei of myelinating oligodendrocytes 5 Fig.

We extracted genomic DNA and measured the 14 C concentration by accelerator mass spectrometry See Supplementary Table 1 for measured 14 C concentrations, associated data and patient information. The 14 C levels increased in owing to above ground nuclear bomb tests, and thereafter declined owing to diffusion and uptake by the biosphere. The vertical lines indicate the date of birth of two individuals, and two hypothetical data points circles of 14 C measured in genomic DNA are placed corresponding to the year of Dynamics of oligodendrocyte generation in multiple sclerosis.

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