title: Nuclei of aged myofibres undergo structural and functional changes suggesting impairment in RNA processing.
abstract: Advancing adult age is associated with a progressive decrease in skeletal muscle mass, strength and quality known as sarcopenia. The mechanisms underlying age-related skeletal muscle wasting and weakness are manifold and still remain to be fully elucidated. Despite the increasing evidence that the progress of muscle diseases leading to muscle atrophy/dystrophy may be related to defective RNA processing, no data on the morpho-functional features of skeletal muscle nuclei in sarcopenia are available at present. In this view, we have investigated, by combining morphometry and immunocytochemistry at light and electron microscopy, the fine structure of myonuclei as well as the distribution and amount of RNA processing factors in skeletal myofibres of biceps brachii and quadriceps femoris from adult and old rats. Results demonstrate that the myonuclei of aged type II fibres show an increased amount of condensed chromatin and lower amounts of phosphorylated polymerase II and DNA/RNA hybrid molecules, clearly indicating a decrease in pre-mRNA transcription rate compared to adult animals. In addition, myonuclei of aged fibres show decreased amounts of nucleoplasmic splicing factors and an accumulation of cleavage factors, polyadenilated RNA and perichromatin granules, suggesting a reduction in the processing and transport rate of premRNA. During ageing, it seems therefore that in rat myonuclei the entire production chain of mRNA, from synthesis to cytoplasmic export, is less efficient. This failure likely contributes to the reduced responsiveness of muscle cells to anabolic stimuli in the elderly.
authors.affiliation: Dipartimento di Scienze Morfologico-Biomediche, Sezione di Anatomia e Istologia, University of Verona, Italy. manuela.malatesta@univr.it
authors.forename: M
authors.initials: M
authors.lastname: Malatesta
authors.forename: F
authors.initials: F
authors.lastname: Perdoni
authors.forename: S
authors.initials: S
authors.lastname: Muller
authors.forename: C
authors.initials: C
authors.lastname: Zancanaro
authors.forename: C
authors.initials: C
authors.lastname: Pellicciari
mesh_terms: D000818:Animals; D002466:Cell Nucleolus / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure*; D016922:Cellular Senescence / Q000502:physiology*; D039241:Cleavage Stimulation Factor / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D018657:Muscle Fibers, Slow-Twitch / Q000166:cytology; D052097:Quadriceps Muscle / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D012313:RNA / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D055517:snRNP Core Proteins / Q000378:metabolism
chemical_list: D039241:Cleavage Stimulation Factor; D012333:RNA, Messenger; D055517:snRNP Core Proteins; D012313:RNA; D004247:DNA; D012319:RNA Polymerase II
references.citation: Muscle Nerve. 2004 Jan;29(1):120-7
references.pmid: 14694507
references.citation: J Mol Biol. 1974 Sep 5;88(1):233-45
references.pmid: 4613842
references.citation: Exp Cell Res. 1996 Dec 15;229(2):189-97
references.pmid: 8986596
references.citation: Am J Clin Nutr. 2002 Aug;76(2):473-81
references.pmid: 12145025
references.citation: Aging Cell. 2005 Apr;4(2):65-77
references.pmid: 15771610
references.citation: Exerc Sport Sci Rev. 2008 Apr;36(2):51-7
references.pmid: 18362685
references.citation: Sci Aging Knowledge Environ. 2003 Nov 19;2003(46):pe31
references.pmid: 14627844
references.citation: J Gerontol A Biol Sci Med Sci. 1995 Nov;50 Spec No:11-6
references.pmid: 7493202
references.citation: Curr Opin Neurol. 2007 Oct;20(5):572-6
references.pmid: 17885447
references.citation: Cell Mol Life Sci. 2002 Nov;59(11):1872-91
references.pmid: 12530519
references.citation: Eur Arch Psychiatry Neurol Sci. 1987;236(4):235-6
references.pmid: 3582433
references.citation: Biol Cell. 2004 Oct;96(8):603-15
references.pmid: 15519695
references.citation: J Gerontol A Biol Sci Med Sci. 2003 Nov;58(11):999-1001
references.pmid: 14630880
references.citation: Ageing Res Rev. 2006 Nov;5(4):402-33
references.pmid: 16831573
references.citation: J Histochem Cytochem. 1994 Jan;42(1):1-10
references.pmid: 7505298
references.citation: Biogerontology. 2008 Aug;9(4):213-28
references.pmid: 18299960
references.citation: Anat Rec. 2000 Mar 1;258(3):305-18
references.pmid: 10705351
references.citation: Eur J Histochem. 2006 Jul-Sep;50(3):177-82
references.pmid: 16920640
references.citation: Biochem Biophys Res Commun. 2002 Jun 7;294(2):354-8
references.pmid: 12051719
references.citation: J Androl. 1997 Mar-Apr;18(2):103-6
references.pmid: 9154502
references.citation: Ann N Y Acad Sci. 2004 Jun;1019:379-82
references.pmid: 15247049
references.citation: Microcirculation. 2006 Jun;13(4):275-7
references.pmid: 16611593
references.citation: Differentiation. 2008 Jan;76(1):57-65
references.pmid: 17697125
references.citation: J Appl Physiol (1985). 2003 Oct;95(4):1728-36
references.pmid: 12970378
references.citation: J Ultrastruct Res. 1981 Mar;74(3):341-50
references.pmid: 7253060
references.citation: Toxicol In Vitro. 2008 Dec;22(8):1853-60
references.pmid: 18835430
references.citation: Eur J Histochem. 2007 Oct-Dec;51(4):305-10
references.pmid: 18162461
references.citation: J Appl Physiol (1985). 2003 Oct;95(4):1717-27
references.pmid: 12970377
references.citation: J Appl Physiol (1985). 2004 Sep;97(3):1082-90
references.pmid: 15121742
references.citation: Annu Rev Cell Dev Biol. 1995;11:93-121
references.pmid: 8689574
references.citation: Acta Physiol (Oxf). 2009 Sep;197(1):55-63
references.pmid: 19254285
references.citation: Biol Cell. 1993;79(1):55-61
references.pmid: 8118411
references.citation: Mol Cell Biol. 2001 Feb;21(4):1228-38
references.pmid: 11158309
references.citation: Curr Top Dev Biol. 2005;68:123-48
references.pmid: 16124998
references.citation: Free Radic Res. 2006 Dec;40(12):1250-8
references.pmid: 17090414
references.citation: Anat Embryol (Berl). 1993 Apr;187(4):363-9
references.pmid: 8512088
references.citation: Curr Med Chem. 2004 May;11(9):1105-12
references.pmid: 15134509
references.citation: Acta Physiol Scand. 1978 May;103(1):31-9
references.pmid: 208350
references.citation: Med Hypotheses. 2004;63(1):83-6
references.pmid: 15193354
references.citation: Biogerontology. 2002;3(5):307-16
references.pmid: 12237567
references.citation: J Ultrastruct Res. 1969 May;27(3):250-65
references.pmid: 4181256
references.citation: Anat Rec. 1995 Dec;243(4):430-7
references.pmid: 8597289
references.citation: Exp Gerontol. 2005 Jun;40(6):473-81
references.pmid: 15935591
references.citation: Eur J Histochem. 2004;48(1):5-14
references.pmid: 15145771
references.citation: Exp Cell Res. 1996 Dec 15;229(2):217-25
references.pmid: 8986601
references.citation: Ann N Y Acad Sci. 2001 Apr;928:65-70
references.pmid: 11795529
references.citation: Jpn J Physiol. 2003 Apr;53(2):145-50
references.pmid: 12877770
references.citation: J Physiol. 2008 Jun 1;586(11):2675-81
references.pmid: 18440990
references.citation: Biochim Biophys Acta. 1990 Nov 30;1087(3):265-92
references.pmid: 2147394
references.citation: Sports Med. 2004;34(12):809-24
references.pmid: 15462613
references.citation: Exp Gerontol. 2009 Jan-Feb;44(1-2):106-11
references.pmid: 18657920
references.citation: Proc Natl Acad Sci U S A. 1975 Aug;72(8):3065-7
references.pmid: 1059092
references.citation: Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E151-7
references.pmid: 16926381
references.citation: Sports Med. 2005;35(6):473-83
references.pmid: 15974633
references.citation: J Appl Physiol (1985). 2006 Jun;100(6):2024-30
references.pmid: 16497845
references.citation: Eur J Histochem. 2008 Oct-Dec;52(4):263-7
references.pmid: 19109102
references.citation: Eur J Clin Nutr. 2000 Jun;54 Suppl 3:S40-7
references.pmid: 11041074
references.citation: BMC Cell Biol. 2009 Mar 14;10:19
references.pmid: 19284674
references.citation: Int J Biochem Cell Biol. 2005 Oct;37(10):1962-73
references.pmid: 15905114
references.citation: Anat Embryol (Berl). 1993 Dec;188(6):515-36
references.pmid: 8129175
references.citation: J Am Geriatr Soc. 1977 Mar;25(3):125-31
references.pmid: 839043
references.citation: J Neurol Sci. 1989 Oct;93(1):105-24
references.pmid: 2809627
references.citation: Curr Opin Hematol. 2001 May;8(3):131-6
references.pmid: 11303144
references.citation: Mech Ageing Dev. 2003 Feb;124(2):175-81
references.pmid: 12633937
references.citation: Curr Opin Clin Nutr Metab Care. 2009 Jan;12(1):37-41
references.pmid: 19057185
references.citation: J Appl Physiol (1985). 2009 Jun;106(6):2040-8
references.pmid: 19131471
references.citation: J Bone Miner Res. 2005 May;20(5):721-9
references.pmid: 15824844
references.citation: Gerontology. 1988;34(3):97-109
references.pmid: 3417154