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Magalhães, João Pedro de

doi:10.1023/a:1023356005749

Cited by 16 publications

(10 citation statements)

References 12 publications

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“…One hypothesis is that the cascade of events that regulates ontogeny fades away after sexual maturity resulting in ageing. This would explain as to why the mammalian ageing process appears as if timed by some unknown mechanism [4].…”

Section: Resultsmentioning

confidence: 99%

“…Despite its general interest not only to the academic community but to medicine and the public in general, human ageing is a poorly understood biological problem [1]. Findings in model organisms have shown that genes can regulate ageing [2,3] and so ageing clearly has a strong genetic component [4]. Yet since studying a process with the duration of ageing in humans is nearly impossible, it is unknown how these genes fit together and impact on human ageing.…”

Section: Introductionmentioning

confidence: 99%

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GenAge: a genomic and proteomic network map of human ageing

Magalhães¹,

Toussaint²

2004

FEBS Letters

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124

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The aim of this work was to provide an overview of the genetics of human ageing to gain novel insights about the mechanisms involved. By incorporating findings from model organisms to humans, such as mutations that either delay or accelerate ageing in mice, we constructed the gene networks previously related to ageing: namely, the network related to DNA metabolism and the network involving the GH/IGF-1 axis. Gathering data about the interacting partners of these proteins allowed us to suggest the involvement in ageing of a number of proteins through a ''guilt-by-association'' methodology. To organize our data, we developed the first curated database of genes related to human ageing: GenAge. With over 200 entries, GenAge may serve as a reference database of genes related to human ageing. Moreover, we rendered the first proteomic network map of human ageing, which suggests a relationship between the genetics of development and the genetics of ageing. Our work serves as a framework upon which a systems-biology understanding of ageing can be developed. GenAge is freely available for academic purposes at: http://genomics.senescence.info/genes/.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GenAge: a genomic and proteomic network map of human ageing

Magalhães¹,

Toussaint²

2004

FEBS Letters

Self Cite

124

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“…Many age-related changes are already described such as hair loss, decreased respiratory and kidney function, and decreased tissue regeneration which leads, for example, to an increased wrinkling of the skin. A single overall mechanism that gradually reduces functional capacity has not yet been identified even though the process of aging is likely to be genetically controlled by a small set of genetic mechanisms [21]. But if it is true that aging has a strong genetic component, it is also true that individual aging is subject to external influences as well.…”

Section: Discussionmentioning

confidence: 99%

A Mesenchymal Stromal Cell Gene Signature for Donor Age

et al. 2012

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Human aging is associated with loss of function and regenerative capacity. Human bone marrow derived mesenchymal stromal cells (hMSCs) are involved in tissue regeneration, evidenced by their capacity to differentiate into several lineages and therefore are considered the golden standard for cell-based regeneration therapy. Tissue maintenance and regeneration is dependent on stem cells and declines with age and aging is thought to influence therapeutic efficacy, therefore, more insight in the process of aging of hMSCs is of high interest. We, therefore, hypothesized that hMSCs might reflect signs of aging. In order to find markers for donor age, early passage hMSCs were isolated from bone marrow of 61 donors, with ages varying from 17–84, and clinical parameters, in vitro characteristics and microarray analysis were assessed. Although clinical parameters and in vitro performance did not yield reliable markers for aging since large donor variations were present, genome-wide microarray analysis resulted in a considerable list of genes correlating with human age. By comparing the transcriptional profile of aging in human with the one from rat, we discovered follistatin as a common marker for aging in both species. The gene signature presented here could be a useful tool for drug testing to rejuvenate hMSCs or for the selection of more potent, hMSCs for cell-based therapy.

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“…Genetic analysis of mortality rate has clearly revealed that ageing has strong genetic components 1 – 4 . Previously identified ageing-related genes are summarized in GenAge, a high quality, manually curated database 5 .…”

Section: Introductionmentioning

confidence: 99%

Prediction and characterization of human ageing-related proteins by using machine learning

Kerepesi

Daróczy

Sturm

et al. 2018

Sci Rep

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Ageing has a huge impact on human health and economy, but its molecular basis – regulation and mechanism – is still poorly understood. By today, more than three hundred genes (almost all of them function as protein-coding genes) have been related to human ageing. Although individual ageing-related genes or some small subsets of these genes have been intensively studied, their analysis as a whole has been highly limited. To fill this gap, for each human protein we extracted 21000 protein features from various databases, and using these data as an input to state-of-the-art machine learning methods, we classified human proteins as ageing-related or non-ageing-related. We found a simple classification model based on only 36 protein features, such as the “number of ageing-related interaction partners”, “response to oxidative stress”, “damaged DNA binding”, “rhythmic process” and “extracellular region”. Predicted values of the model quantify the relevance of a given protein in the regulation or mechanisms of the human ageing process. Furthermore, we identified new candidate proteins having strong computational evidence of their important role in ageing. Some of them, like Cytochrome b-245 light chain (CY24A) and Endoribonuclease ZC3H12A (ZC12A) have no previous ageing-associated annotations.

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Cited by 16 publications

References 12 publications

GenAge: a genomic and proteomic network map of human ageing

GenAge: a genomic and proteomic network map of human ageing

A Mesenchymal Stromal Cell Gene Signature for Donor Age

Prediction and characterization of human ageing-related proteins by using machine learning

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