Nuclei of aged myofibres undergo structural and functional changes suggesting impairment in RNA processing.
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.
Malatesta
M
M
Dipartimento di Scienze Morfologico-Biomediche, Sezione di Anatomia e Istologia, University of Verona, Italy. manuela.malatesta@univr.it
Perdoni
F
F
Muller
S
S
Zancanaro
C
C
Pellicciari
C
C
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
D039241:Cleavage Stimulation Factor; D012333:RNA, Messenger; D055517:snRNP Core Proteins; D012313:RNA; D004247:DNA; D012319:RNA Polymerase II
Muscle Nerve. 2004 Jan;29(1):120-7
14694507
J Mol Biol. 1974 Sep 5;88(1):233-45
4613842
Exp Cell Res. 1996 Dec 15;229(2):189-97
8986596
Am J Clin Nutr. 2002 Aug;76(2):473-81
12145025
Aging Cell. 2005 Apr;4(2):65-77
15771610
Exerc Sport Sci Rev. 2008 Apr;36(2):51-7
18362685
Sci Aging Knowledge Environ. 2003 Nov 19;2003(46):pe31
14627844
J Gerontol A Biol Sci Med Sci. 1995 Nov;50 Spec No:11-6
7493202
Curr Opin Neurol. 2007 Oct;20(5):572-6
17885447
Cell Mol Life Sci. 2002 Nov;59(11):1872-91
12530519
Eur Arch Psychiatry Neurol Sci. 1987;236(4):235-6
3582433
Biol Cell. 2004 Oct;96(8):603-15
15519695
J Gerontol A Biol Sci Med Sci. 2003 Nov;58(11):999-1001
14630880
Ageing Res Rev. 2006 Nov;5(4):402-33
16831573
J Histochem Cytochem. 1994 Jan;42(1):1-10
7505298
Biogerontology. 2008 Aug;9(4):213-28
18299960
Anat Rec. 2000 Mar 1;258(3):305-18
10705351
Eur J Histochem. 2006 Jul-Sep;50(3):177-82
16920640
Biochem Biophys Res Commun. 2002 Jun 7;294(2):354-8
12051719
J Androl. 1997 Mar-Apr;18(2):103-6
9154502
Ann N Y Acad Sci. 2004 Jun;1019:379-82
15247049
Microcirculation. 2006 Jun;13(4):275-7
16611593
Differentiation. 2008 Jan;76(1):57-65
17697125
J Appl Physiol (1985). 2003 Oct;95(4):1728-36
12970378
J Ultrastruct Res. 1981 Mar;74(3):341-50
7253060
Toxicol In Vitro. 2008 Dec;22(8):1853-60
18835430
Eur J Histochem. 2007 Oct-Dec;51(4):305-10
18162461
J Appl Physiol (1985). 2003 Oct;95(4):1717-27
12970377
J Appl Physiol (1985). 2004 Sep;97(3):1082-90
15121742
Annu Rev Cell Dev Biol. 1995;11:93-121
8689574
Acta Physiol (Oxf). 2009 Sep;197(1):55-63
19254285
Biol Cell. 1993;79(1):55-61
8118411
Mol Cell Biol. 2001 Feb;21(4):1228-38
11158309
Curr Top Dev Biol. 2005;68:123-48
16124998
Free Radic Res. 2006 Dec;40(12):1250-8
17090414
Anat Embryol (Berl). 1993 Apr;187(4):363-9
8512088
Curr Med Chem. 2004 May;11(9):1105-12
15134509
Acta Physiol Scand. 1978 May;103(1):31-9
208350
Med Hypotheses. 2004;63(1):83-6
15193354
Biogerontology. 2002;3(5):307-16
12237567
J Ultrastruct Res. 1969 May;27(3):250-65
4181256
Anat Rec. 1995 Dec;243(4):430-7
8597289
Exp Gerontol. 2005 Jun;40(6):473-81
15935591
Eur J Histochem. 2004;48(1):5-14
15145771
Exp Cell Res. 1996 Dec 15;229(2):217-25
8986601
Ann N Y Acad Sci. 2001 Apr;928:65-70
11795529
Jpn J Physiol. 2003 Apr;53(2):145-50
12877770
J Physiol. 2008 Jun 1;586(11):2675-81
18440990
Biochim Biophys Acta. 1990 Nov 30;1087(3):265-92
2147394
Sports Med. 2004;34(12):809-24
15462613
Exp Gerontol. 2009 Jan-Feb;44(1-2):106-11
18657920
Proc Natl Acad Sci U S A. 1975 Aug;72(8):3065-7
1059092
Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E151-7
16926381
Sports Med. 2005;35(6):473-83
15974633
J Appl Physiol (1985). 2006 Jun;100(6):2024-30
16497845
Eur J Histochem. 2008 Oct-Dec;52(4):263-7
19109102
Eur J Clin Nutr. 2000 Jun;54 Suppl 3:S40-7
11041074
BMC Cell Biol. 2009 Mar 14;10:19
19284674
Int J Biochem Cell Biol. 2005 Oct;37(10):1962-73
15905114
Anat Embryol (Berl). 1993 Dec;188(6):515-36
8129175
J Am Geriatr Soc. 1977 Mar;25(3):125-31
839043
J Neurol Sci. 1989 Oct;93(1):105-24
2809627
Curr Opin Hematol. 2001 May;8(3):131-6
11303144
Mech Ageing Dev. 2003 Feb;124(2):175-81
12633937
Curr Opin Clin Nutr Metab Care. 2009 Jan;12(1):37-41
19057185
J Appl Physiol (1985). 2009 Jun;106(6):2040-8
19131471
J Bone Miner Res. 2005 May;20(5):721-9
15824844
Gerontology. 1988;34(3):97-109
3417154