Organ Specificity

Publication Title: 
Nature

The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages.

Author(s): 
Herndon, Laura A.
Schmeissner, Peter J.
Dudaronek, Justyna M.
Brown, Paula A.
Listner, Kristin M.
Sakano, Yuko
Paupard, Marie C.
Hall, David H.
Driscoll, Monica
Publication Title: 
Ageing Research Reviews

Multicellular organisms are composed of an interactive network of various tissues that are functionally organized as discrete organs. If aging were slowed in a specific tissue or organ how would that impact longevity at the organismal level? In recent years, molecular genetic approaches in invertebrate model systems have dramatically improved our understanding of the aging process and have provided insight into the preceding question.

Author(s): 
Rera, Michael
Azizi, Masoud J.
Walker, David W.
Publication Title: 
European journal of human genetics: EJHG

Spinal muscular atrophy (SMA) is the leading genetic cause of early childhood death worldwide and no therapy is available today. Many drugs, especially histone deacetylase inhibitors (HDACi), increase SMN levels. As all HDACi tested so far only mildly ameliorate the SMA phenotype or are unsuitable for use in humans, there is still need to identify more potent drugs. Here, we assessed the therapeutic power of the pan-HDACi JNJ-26481585 for SMA, which is currently used in various clinical cancer trials.

Author(s): 
Schreml, Julia
Riessland, Markus
Paterno, Mario
Garbes, Lutz
Roflbach, Kristina
Ackermann, Bastian
Kr‰mer, Jan
Somers, Eilidh
Parson, Simon H.
Heller, Raoul
Berkessel, Albrecht
Sterner-Kock, Anja
Wirth, Brunhilde
Publication Title: 
Disease Models & Mechanisms

Cardiac fibrosis is critically involved in the adverse remodeling accompanying dilated cardiomyopathies (DCMs), which leads to cardiac dysfunction and heart failure (HF). Connective tissue growth factor (CTGF), a profibrotic cytokine, plays a key role in this deleterious process. Some beneficial effects of IGF1 on cardiomyopathy have been described, but its potential role in improving DCM is less well characterized.

Author(s): 
Touvron, Melissa
Escoubet, Brigitte
Mericskay, Mathias
Angelini, Aude
Lamotte, Luciane
Santini, Maria Paola
Rosenthal, Nadia
Daegelen, Dominique
Tuil, David
Decaux, Jean-FranÁois
Publication Title: 
Ageing Research Reviews

Multicellular organisms are composed of an interactive network of various tissues that are functionally organized as discrete organs. If aging were slowed in a specific tissue or organ how would that impact longevity at the organismal level? In recent years, molecular genetic approaches in invertebrate model systems have dramatically improved our understanding of the aging process and have provided insight into the preceding question.

Author(s): 
Rera, Michael
Azizi, Masoud J.
Walker, David W.
Publication Title: 
The EMBO journal

Lifespan of C. elegans is affected by the nervous system; however, the underlying neural integration still remains unclear. In this work, we targeted an antagonistic neural system consisting of low-oxygen sensing BAG neurons and high-oxygen sensing URX neurons. While ablation of BAG neurons increases lifespan of C. elegans, ablation of URX neurons decreases lifespan. Genetic analysis revealed that BAG and URX neurons counterbalance each other via different guanylate cyclases (GCYs) to control lifespan balance.

Author(s): 
Liu, Tiewen
Cai, Dongsheng
Publication Title: 
Developmental Cell

Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. Caenorhabditis elegans DRE-1/FBXO11 functions in an SCF E3-ubiquitin ligase complex to regulate the transition to adult programs, but its cognate proteolytic substrates are unknown. Here, we identify the conserved transcription factor BLMP-1 as a substrate of the SCF(DRE-1/FBXO11) complex. blmp-1 deletion suppressed dre-1 mutant phenotypes and exhibited developmental timing defects opposite to dre-1.

Author(s): 
Horn, Moritz
Geisen, Christoph
Cermak, Lukas
Becker, Ben
Nakamura, Shuhei
Klein, Corinna
Pagano, Michele
Antebi, Adam
Publication Title: 
Free Radical Biology & Medicine

Energy restriction (ER), without malnutrition, increases maximum life span and retards the development of a broad array of pathophysiological changes in laboratory rodents. The mechanism responsible for the retardation of aging by ER is, however, unknown. One proposed explanation is a reduction in energy expenditure (EE). Reduced EE may increase life span by decreasing the number of oxygen molecules interacting with mitochondria, thereby lowering reactive oxygen species (ROS) production. As a step toward testing this hypothesis, it is important to determine the effect of ER on EE.

Author(s): 
Ramsey, J. J.
Harper, M. E.
Weindruch, R.
Publication Title: 
Cell Stem Cell

Calorie restriction (CR) extends life span and ameliorates age-related pathologies in most species studied, yet the mechanisms underlying these effects remain unclear. Using mouse skeletal muscle as a model, we show that CR acts in part by enhancing the function of tissue-specific stem cells. Even short-term CR significantly enhanced stem cell availability and activity in the muscle of young and old animals, in concert with an increase in mitochondrial abundance and induction of conserved metabolic and longevity regulators.

Author(s): 
Cerletti, Massimiliano
Jang, Young C.
Finley, Lydia W. S.
Haigis, Marcia C.
Wagers, Amy J.
Publication Title: 
Cell Metabolism

Iron regulatory proteins (Irps) 1 and 2 posttranscriptionally control the expression of transcripts that contain iron-responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor, and hypoxia-inducible factor 2? (HIF2?). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low-iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2?

Author(s): 
Ghosh, Manik C.
Zhang, De-Liang
Jeong, Suh Young
Kovtunovych, Gennadiy
Ollivierre-Wilson, Hayden
Noguchi, Audrey
Tu, Tiffany
Senecal, Thomas
Robinson, Gabrielle
Crooks, Daniel R.
Tong, Wing-Hang
Ramaswamy, Kavitha
Singh, Anamika
Graham, Brian B.
Tuder, Rubin M.
Yu, Zu-Xi
Eckhaus, Michael
Lee, Jaekwon
Springer, Danielle A.
Rouault, Tracey A.

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