| 1. |
|
|
| 2. |
- Sandri, M, et al.
(author)
-
Signalling pathways regulating muscle mass in ageing skeletal muscle : The role of the IGF1-Akt-mTOR-FoxO pathway
- 2013
-
In: Biogerontology (Dordrecht). - : Springer Science and Business Media LLC. - 1389-5729 .- 1573-6768. ; 14:3 SI, s. 303-323
-
Journal article (peer-reviewed)abstract
- During ageing skeletal muscles undergo a process of structural and functional remodelling that leads to sarcopenia, a syndrome characterized by loss of muscle mass and force and a major cause of physical frailty. To determine the causes of sarcopenia and identify potential targets for interventions aimed at mitigating ageing-dependent muscle wasting, we focussed on the main signalling pathway known to control protein turnover in skeletal muscle, consisting of the insulin-like growth factor 1 (IGF1), the kinase Akt and its downstream effectors, the mammalian target of rapamycin (mTOR) and the transcription factor FoxO. Expression analyses at the transcript and protein level, carried out on well-characterized cohorts of young, old sedentary and old active individuals and on mice aged 200, 500 and 800 days, revealed only modest age-related differences in this pathway. Our findings suggest that during ageing there is no downregulation of IGF1/Akt pathway and that sarcopenia is not due to FoxO activation and upregulation of the proteolytic systems. A potentially interesting result was the increased phosphorylation of the ribosomal protein S6, indicative of increased activation of mTOR complex1 (mTORC1), in aged mice. This result may provide the rationale why rapamycin treatment and caloric restriction promote longevity, since both interventions blunt activation of mTORC1; however, this change was not statistically significant in humans. Finally, genetic perturbation of these pathways in old mice aimed at promoting muscle hypertrophy via Akt overexpression or preventing muscle loss through inactivation of the ubiquitin ligase atrogin1 were found to paradoxically cause muscle pathology and reduce lifespan, suggesting that drastic activation of the IGF1-Akt pathway may be counterproductive, and that sarcopenia is accelerated, not delayed, when protein degradation pathways are impaired.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Prezza, N., et al.
(author)
-
ERNE-BS5 : Aligning BS-treated sequences by multiple hits on a 5-letters alphabet
- 2012
-
In: BCB '12 Proceedings of the ACM Conference on Bioinformatics, Computational Biology and Biomedicine. - New York, NY, USA : ACM. - 9781450316705 ; , s. 12-19
-
Conference paper (peer-reviewed)abstract
- Cytosine methylation is a DNA modification that has great impact on the regulation of gene expression and important implications for the biology and health of several living beings, including humans. Bisulfite conversion followed by next generation sequencing (BS-seq) of DNA is the gold standard technique used to detect DNA methylation at single-base resolution on a genome scale through the identification of 5-methylcytosine (5-mC). However, by converting unmethylated cytosines into thymines, BS-seq poses computational challenges to read alignment and aggravates the issue of multiple hits due to the ambiguity raised by the reduced sequence complexity. Here we present ERNE-BS5 (Extended Randomized Numerical alignEr - BiSulfite 5 ), an aligning program developed to efficiently map BS-treated reads against large genomes (e.g., human). To achieve this goal we have implemented three different ideas: (i) we use a 5-letters alphabet for storing methylation information, (ii) we use a weighted context-aware Hamming distance to identify a T coming from an unmethylated C context, and (iii) we use an iterative process to position multiple-hit reads starting from a preliminary map built using single-hit alignments. The map is corrected and extended at each cycle using the alignments added in the previous iteration. ERNE-BS5 is based on a new improved version of the rNA [20] aligning software with a more efficient core. ERNE (Extended Randomized Numerical alignEr) is a short string alignment package whose goal is to provide an all-inclusive set of tools to handle short reads. ERNE comprises: ERNE-MAP, ERNE-DMAP, ERNEFILTER, ERNE-VISUAL, and, from now on, ERNE-BS5. ERNE is free software and distributed with an Open Source License (GPL V3) and can be downloaded at: http://erne.sourceforge.net.
|
|
