Computational Biology

Publication Title: 
FEBS letters

Strains of Caenorhabditis elegans mutant for clk-1 exhibit a 20-40% increase in mean lifespan. clk-1 encodes a mitochondrial protein thought to be either an enzyme or regulatory molecule acting within the ubiquinone biosynthesis pathway. Here CLK-1 is shown to be related to the ubiquinol oxidase, alternative oxidase, and belong to the functionally diverse di-iron-carboxylate protein family which includes bacterioferritin and methane mono-oxygenase.

Author(s): 
Rea, S.
Publication Title: 
Aging Cell

This annual review focuses on invertebrate model organisms, which shed light on new mechanisms in aging and provide excellent systems for both genome-wide and in-depth analysis. This year, protein interaction networks have been used in a new bioinformatic approach to identify novel genes that extend replicative lifespan in yeast. In an extended approach, using a new, human protein interaction network, information from the invertebrates was used to identify new, candidate genes for lifespan extension and their orthologues were validated in the nematode Caenorhabditis elegans.

Author(s): 
Partridge, Linda
Publication Title: 
BMC bioinformatics

BACKGROUND: Differential coexpression is a change in coexpression between genes that may reflect 'rewiring' of transcriptional networks. It has previously been hypothesized that such changes might be occurring over time in the lifespan of an organism. While both coexpression and differential expression of genes have been previously studied in life stage change or aging, differential coexpression has not. Generalizing differential coexpression analysis to many time points presents a methodological challenge.

Author(s): 
Gillis, Jesse
Pavlidis, Paul
Publication Title: 
Cell Cycle (Georgetown, Tex.)

Macroautophagy is a self-cannibalistic process that enables cells to adapt to various stresses and maintain energy homeostasis. Additionally, autophagy is an important route for turnover of misfolded proteins and damaged organelles, with important implications in cancer, neurodegenerative diseases and aging. Resveratrol and spermidine are able to induce autophagy by affecting deacetylases and acetylases, respectively, and have been found to extend the life-span of model organisms.

Author(s): 
Bennetzen, Martin V.
MariÒo, Guillermo
Pultz, Dennis
Morselli, Eugenia
FÊrgeman, Nils J.
Kroemer, Guido
Andersen, Jens S.
Publication Title: 
PloS One

Aging in the world population has increased every year. Superoxide dismutase 2 (Mn-SOD or SOD2) protects against oxidative stress, a main factor influencing cellular longevity. Polymorphisms in SOD2 have been associated with the development of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, as well as psychiatric disorders, such as schizophrenia, depression and bipolar disorder.

Author(s): 
de Carvalho, Mariana Dias Castela
De Mesquita, Joelma Freire
Publication Title: 
Nature Genetics

Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders.

Author(s): 
Styrkarsdottir, Unnur
Thorleifsson, Gudmar
Helgadottir, Hafdis T.
Bomer, Nils
Metrustry, Sarah
Bierma-Zeinstra, S.
Strijbosch, Annelieke M.
Evangelou, Evangelos
Hart, Deborah
Beekman, Marian
Jonasdottir, Aslaug
Sigurdsson, Asgeir
Eiriksson, Finnur F.
Thorsteinsdottir, Margret
Frigge, Michael L.
Kong, Augustine
Gudjonsson, Sigurjon A.
Magnusson, Olafur T.
Masson, Gisli
TREAT-OA Consortium
arcOGEN Consortium
Hofman, Albert
Arden, Nigel K.
Ingvarsson, Thorvaldur
Lohmander, Stefan
Kloppenburg, Margreet
Rivadeneira, Fernando
Nelissen, Rob G. H. H.
Spector, Tim
Uitterlinden, Andre
Slagboom, P. Eline
Thorsteinsdottir, Unnur
Jonsdottir, Ingileif
Valdes, Ana M.
Meulenbelt, Ingrid
van Meurs, Joyce
Jonsson, Helgi
Stefansson, Kari
Publication Title: 
Aging Cell

This annual review focuses on invertebrate model organisms, which shed light on new mechanisms in aging and provide excellent systems for both genome-wide and in-depth analysis. This year, protein interaction networks have been used in a new bioinformatic approach to identify novel genes that extend replicative lifespan in yeast. In an extended approach, using a new, human protein interaction network, information from the invertebrates was used to identify new, candidate genes for lifespan extension and their orthologues were validated in the nematode Caenorhabditis elegans.

Author(s): 
Partridge, Linda
Publication Title: 
Aging Cell

Silent information regulator 2 (Sir2) orthologs are an evolutionarily conserved family of NAD-dependent protein deacetylases that regulate aging and longevity in model organisms. The mammalian Sir2 ortholog Sirt1 regulates metabolic and stress responses through the deacetylation of many transcriptional regulatory factors.

Author(s): 
Grimm, Andrew A.
Brace, Cynthia S.
Wang, Ting
Stormo, Gary D.
Imai, Shin-ichiro
Publication Title: 
Translational Psychiatry

Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans. It is typified by highly variable symptoms, which might be explained by epigenetic regulation of genes in the interval. Using computational algorithms, our laboratory previously predicted that DiGeorge critical region 6 (DGCR6), which lies within the deletion interval, is imprinted in humans. Expression and epigenetic regulation of this gene have not, however, been examined in 22q11DS subjects.

Author(s): 
Das Chakraborty, R.
Chakraborty, D.
Bernal, A. J.
Schoch, K.
Howard, T. D.
Ip, E. H.
Hooper, S. R.
Keshavan, M. S.
Jirtle, R. L.
Shashi, V.
Publication Title: 
BMC genomics

BACKGROUND: As the most stable and experimentally accessible epigenetic mark, DNA methylation is of great interest to the research community. The landscape of DNA methylation across tissues, through development and in disease pathogenesis is not yet well characterized. Thus there is a need for rapid and cost effective methods for assessing genome-wide levels of DNA methylation.

Author(s): 
Pidsley, Ruth
Y Wong, Chloe C.
Volta, Manuela
Lunnon, Katie
Mill, Jonathan
Schalkwyk, Leonard C.

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