Carrier Proteins

Publication Title: 
Human Molecular Genetics

The CISD2 gene, which is an evolutionarily conserved novel gene, encodes a transmembrane protein primarily associated with the mitochondrial outer membrane. Significantly, the CISD2 gene is located within the candidate region on chromosome 4q where a genetic component for human longevity has been mapped. Previously, we have shown that Cisd2 deficiency shortens lifespan resulting in premature aging in mice. Additionally, an age-dependent decrease in Cisd2 expression has been detected during normal aging.

Author(s): 
Wu, Chia-Yu
Chen, Yi-Fan
Wang, Chih-Hao
Kao, Cheng-Heng
Zhuang, Hui-Wen
Chen, Chih-Cheng
Chen, Liang-Kung
Kirby, Ralph
Wei, Yau-Huei
Tsai, Shih-Feng
Tsai, Ting-Fen
Publication Title: 
Neurobiology of Aging

A number of neurological diseases are caused by mutations of RNA metabolism-related genes. A complicating issue is that whether under- or overfunction of such genes is responsible for the phenotype. Polyglutamine tract binding protein-1, a causative gene for X-linked mental retardation, is also involved in RNA metabolism, and both mutation and duplication of the gene were reported in human patients. In this study, we first report a novel phenotype of dPQBP1 (drosophila homolog of Polyglutamine tract binding protein-1)-mutant flies, lifespan shortening.

Author(s): 
Tamura, Takuya
Sone, Masaki
Nakamura, Yoko
Shimamura, Teppei
Imoto, Seiya
Miyano, Satoru
Okazawa, Hitoshi
Publication Title: 
The FEBS journal

Lipocalins are a family of proteins characterized by a conserved eight-stranded ?-barrel structure with a ligand-binding pocket. They perform a wide range of biological functions and this functional multiplicity must relate to the lipid partner involved. Apolipoprotein D (ApoD) and its insect homologues, Lazarillo (Laz) and neural Lazarillo (NLaz), share common ancestral functions like longevity, stress resistance and lipid metabolism regulation, coexisting with very specialized functions, like courtship behavior.

Author(s): 
Ruiz, Mario
Sanchez, Diego
Correnti, Colin
Strong, Roland K.
Ganfornina, Maria D.
Publication Title: 
The International Journal of Biochemistry & Cell Biology

Calorie-restricted feeding retards the rate of ageing in mammalian and invertebrate species. The molecular mechanisms underlying this effect include a lower rate of accrual of tissue oxidative damage that is associated with a significantly lower rate of mitochondrial free radical generation in rodent species. To identify the important sites of control and regulation for mitochondrial free radical generation during ageing and calorie-restricted feeding, metabolic control analysis is being applied to the study of mitochondrial bioenergetics.

Author(s): 
Merry, B. J.
Publication Title: 
Aging Cell

Loss of nonshivering thermogenesis in mice by inactivation of the mitochondrial uncoupling protein gene (Ucp1-/- mice) causes increased sensitivity to cold and unexpected resistance to diet-induced obesity at a young age. To clarify the role of UCP1 in body weight regulation throughout life and influence of UCP1 deficiency on longevity, we longitudinally analyzed the phenotypes of Ucp1-/- mice maintained in a room at 23 degrees C.

Author(s): 
Kontani, Y.
Wang, Y.
Kimura, K.
Inokuma, K.-I.
Saito, M.
Suzuki-Miura, T.
Wang, Z.
Sato, Y.
Mori, N.
Yamashita, H.
Publication Title: 
Annual Review of Nutrition

Nutrigenomics refers to the complex effects of the nutritional environment on the genome, epigenome, and proteome of an organism. The diverse tissue- and organ-specific effects of diet include gene expression patterns, organization of the chromatin, and protein post-translational modifications. Long-term effects of diet range from obesity and associated diseases such as diabetes and cardiovascular disease to increased or decreased longevity.

Author(s): 
Ruden, Douglas M.
De Luca, Maria
Garfinkel, Mark D.
Bynum, Kerry L.
Lu, Xiangyi
Publication Title: 
Experimental Gerontology

Apolipoprotein D (ApoD), a member of the Lipocalin family, is the gene most up-regulated with age in the mammalian brain. Its expression strongly correlates with aging-associated neurodegenerative and metabolic diseases. Two homologues of ApoD expressed in the Drosophila brain, Glial Lazarillo (GLaz) and Neural Lazarillo (NLaz), are known to alter longevity in male flies. However, sex differences in the aging process have not been explored so far for these genes.

Author(s): 
Ruiz, Mario
Sanchez, Diego
Canal, Inmaculada
Acebes, Angel
Ganfornina, Maria D.
Publication Title: 
Current biology: CB

BACKGROUND: Telomerase is a ribonucleoprotein that copies a short RNA template into telomeric DNA, maintaining eukaryotic chromosome ends and preventing replicative senescence. Telomeres differentiate chromosome ends from DNA double-stranded breaks. Nevertheless, the DNA damage-responsive ATM kinases Tel1p and Mec1p are required for normal telomere maintenance in Saccharomyces cerevisiae. We tested whether the ATM kinases are required for telomerase enzyme activity or whether it is their action on the telomere that allows telomeric DNA synthesis.

Author(s): 
Chan, S. W.
Chang, J.
Prescott, J.
Blackburn, E. H.
Publication Title: 
Molecular Biology of the Cell

In Saccharomyces cerevisiae, telomeric DNA is protected by a nonnucleosomal protein complex, tethered by the protein Rap1. Rif and Sir proteins, which interact with Rap1p, are thought to have further interactions with conventional nucleosomic chromatin to create a repressive structure that protects the chromosome end.

Author(s): 
Smith, C. D.
Smith, D. L.
DeRisi, J. L.
Blackburn, E. H.
Publication Title: 
Mammalian Genome: Official Journal of the International Mammalian Genome Society

Prader-Willi syndrome (PWS) results from loss of function of a 1.0- to 1.5-Mb domain of imprinted, paternally expressed genes in human Chromosome (Chr) 15q11-q13. The loss of imprinted gene expression in the homologous region in mouse Chr 7C leads to a similar neonatal PWS phenotype. Several protein-coding genes in the human PWS region are intronless, possibly arising by retrotransposition. Here we present evidence for continued acquisition of genes by the mouse PWS region during evolution.

Author(s): 
Chai, J. H.
Locke, D. P.
Ohta, T.
Greally, J. M.
Nicholls, R. D.

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