title: Mitochondrial adaptations evoked with exercise are associated with a reduction in age-induced testicular atrophy in Fischer-344 rats.
abstract: Mitochondrial dysfunction in various tissues has been associated with numerous conditions including aging. In testes, aging induces atrophy and a decline in male reproductive function but the involvement of mitochondria is not clear. The purpose of this study was to examine whether the mitochondrial profile differed with (1) aging, and (2) 10-weeks of treadmill exercise training, in the testes of young (6 month) and old (24 month) Fischer-344 (F344) animals. Old animals exhibited significant atrophy (30 % decline; P < 0.05) in testes compared to young animals. However, relative mitochondrial content was not reduced with age and this was consistent with the lack of change in the mitochondrial biogenesis regulator protein, peroxisome proliferator-activated receptor gamma coactivator 1-alpha and its downstream targets nuclear respiratory factor-1 and mitochondrial transcription factor A. No effect was observed in the pro- or anti-apoptotic proteins, Bax and Bcl-2, respectively, but age increased apoptosis inducing factor levels. Endurance training induced beneficial mitochondrial adaptations that were more prominent in old animals including greater increases in relative mtDNA content, biogenesis/remodeling (mitofusin 2), antioxidant capacity (mitochondrial superoxide dismutase) and lower levels of phosphorylated histone H2AX, an early marker of DNA damage (P < 0.05). Importantly, these exercise-induced changes were associated with an attenuation of testes atrophy in older sedentary animals (P < 0.05). Our results indicate that aging-induced atrophy in testes may not be associated with changes in relative mitochondrial content and key regulatory proteins and that exercise started in late-life elicits beneficial changes in mitochondria that may protect against age-induced testicular atrophy.
authors.affiliation: Institute on Aging, Department of Aging and Geriatric Research, College of Medicine, University of Florida, Gainesville, FL, 32611, USA.
authors.forename: A-M
authors.initials: AM
authors.lastname: Joseph
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, 32611, USA.
authors.forename: L M-D
authors.initials: LM
authors.lastname: Nguyen
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, 32611, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Welter
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, 32611, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Dominguez
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, 32611, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Behnke
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, 32611, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Adhihetty
mesh_terms: D000222:Adaptation, Physiological; D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001284:Atrophy; D004272:DNA, Mitochondrial / Q000235:genetics; D020935:MAP Kinase Signaling System; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D051265:NF-E2-Related Factor 1 / Q000378:metabolism; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D005082:Physical Exertion / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D013737:Testis / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D051265:NF-E2-Related Factor 1; C495632:Nfe2l1 protein, rat; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D000255:Adenosine Triphosphate
references.citation: Cell Metab. 2005 Jun;1(6):361-70
references.pmid: 16054085
references.citation: Hum Reprod Update. 1999 Mar-Apr;5(2):108-19
references.pmid: 10336016
references.citation: J Biol Chem. 2005 Apr 22;280(16):16456-60
references.pmid: 15716268
references.citation: J Clin Endocrinol Metab. 1991 Aug;73(2):221-4
references.pmid: 1856256
references.citation: Hum Reprod. 1993 Nov;8(11):1863-8
references.pmid: 8288752
references.citation: J Clin Endocrinol Metab. 2005 May;90(5):2618-23
references.pmid: 15687322
references.citation: Eur J Endocrinol. 1998 Mar;138(3):322-7
references.pmid: 9539308
references.citation: J Anat. 1976 Apr;121(Pt 2):279-90
references.pmid: 931781
references.citation: Cell Tissue Res. 1979 Jan 30;196(1):1-22
references.pmid: 421242
references.citation: Endocrinology. 1979 Sep;105(3):842-5
references.pmid: 467341
references.citation: J Urol. 2006 Jul;176(1):222-6
references.pmid: 16753405
references.citation: J Intern Med. 2008 Feb;263(2):167-78
references.pmid: 18226094
references.citation: J Physiol. 2005 Aug 15;567(Pt 1):349-58
references.pmid: 15961417
references.citation: Eur J Appl Physiol Occup Physiol. 1998 Oct;78(5):417-21
references.pmid: 9809842
references.citation: Dev Genet. 1995;16(2):95-103
references.pmid: 7736670
references.citation: FASEB J. 2006 Apr;20(6):791-3
references.pmid: 16459353
references.citation: Diabetes. 2003 Aug;52(8):1888-96
references.pmid: 12882902
references.citation: Free Radic Biol Med. 2004 Jan 1;36(1):27-39
references.pmid: 14732288
references.citation: FEBS Lett. 2008 Dec 24;582(30):4191-6
references.pmid: 19041646
references.citation: Nature. 1996 Sep 19;383(6597):224
references.pmid: 8805695
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16501-6
references.pmid: 15546993
references.citation: J Cell Sci. 2010 Aug 1;123(Pt 15):2533-42
references.pmid: 20940129
references.citation: Mol Reprod Dev. 1994 Mar;37(3):345-62
references.pmid: 8185940
references.citation: Am J Physiol Endocrinol Metab. 2006 Jun;290(6):E1145-54
references.pmid: 16403780
references.citation: Biol Reprod Suppl. 1970;2:90-127
references.pmid: 12254595
references.citation: Aging (Milano). 1998 Dec;10(6):497-501
references.pmid: 10078320
references.citation: Cell. 1999 Jul 9;98(1):115-24
references.pmid: 10412986
references.citation: Biol Reprod. 1972 Feb;6(1):136-47
references.pmid: 5014040
references.citation: Anticancer Agents Med Chem. 2008 Apr;8(3):305-12
references.pmid: 18393789
references.citation: Annu Rev Genet. 2005;39:359-407
references.pmid: 16285865
references.citation: J Biol Chem. 2006 Jul 14;281(28):19000-8
references.pmid: 16670093
references.citation: PLoS One. 2013 Jul 23;8(7):e69327
references.pmid: 23935986
references.citation: Am J Physiol Cell Physiol. 2009 Jul;297(1):C217-25
references.pmid: 19439529
references.citation: Mol Cell Biochem. 2008 Jan;307(1-2):23-30
references.pmid: 17805943
references.citation: Eur J Appl Physiol Occup Physiol. 1996;73(1-2):61-5
references.pmid: 8861670
references.citation: J Gerontol. 1979 Jan;34(1):21-7
references.pmid: 759488
references.citation: J Clin Endocrinol Metab. 2001 Nov;86(11):5547-53
references.pmid: 11701734
references.citation: J Appl Physiol (1985). 2005 Jul;99(1):204-9
references.pmid: 15774698
references.citation: Free Radic Biol Med. 2008 Jan 15;44(2):224-9
references.pmid: 18191758
references.citation: Fertil Steril. 2009 Dec;92(6):1941-6
references.pmid: 19013565
references.citation: Aging Cell. 2008 Jan;7(1):2-12
references.pmid: 18028258
references.citation: Int J Sports Med. 2006 Sep;27(9):680-9
references.pmid: 16944397
references.citation: Cell Mol Life Sci. 1997 Feb;53(2):191-7
references.pmid: 9118007
references.citation: Am J Epidemiol. 1998 Apr 15;147(8):750-4
references.pmid: 9554416
references.citation: Biochem Biophys Res Commun. 2011 Apr 29;408(1):180-5
references.pmid: 21501593
references.citation: J Am Geriatr Soc. 2006 Dec;54(12):1832-8
references.pmid: 17198487
references.citation: Clin Chem. 1998 Aug;44(8 Pt 1):1616-20
references.pmid: 9702947
references.citation: FASEB J. 2010 Apr;24(4):1003-14
references.pmid: 19906680
references.citation: Nat Med. 1997 Feb;3(2):124-5
references.pmid: 9018221
references.citation: Biol Chem. 2013 Mar;394(3):393-414
references.pmid: 23154422
references.citation: Nature. 2006 Nov 16;444(7117):337-42
references.pmid: 17086191
references.citation: Int J Impot Res. 2008 Jul-Aug;20(4):378-87
references.pmid: 18480825
references.citation: J Appl Physiol (1985). 2001 Mar;90(3):1137-57
references.pmid: 11181630
references.citation: J Cell Biochem. 2006 Mar 1;97(4):673-83
references.pmid: 16329141
references.citation: Exp Gerontol. 2013 Sep;48(9):869-80
references.pmid: 23751407
references.citation: J Gerontol A Biol Sci Med Sci. 2002 Feb;57(2):M76-99
references.pmid: 11818427
references.citation: Aging Cell. 2009 Aug;8(4):394-404
references.pmid: 19416128
references.citation: Can J Appl Physiol. 2002 Aug;27(4):349-95
references.pmid: 12442352
references.citation: Tohoku J Exp Med. 1969 Nov;99(3):269-80
references.pmid: 5363446
references.citation: Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):517-28
references.pmid: 16677096
references.citation: Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R801-10
references.pmid: 21677264
references.citation: Mol Cell Endocrinol. 2009 Feb 5;299(1):2-13
references.pmid: 19059459
references.citation: Muscle Nerve. 2013 Dec;48(6):963-70
references.pmid: 23494933
references.citation: J Clin Endocrinol Metab. 1968 Sep;28(9):1347-55
references.pmid: 5679997
references.citation: Gerontology. 1980;26(4):221-30
references.pmid: 7372101
references.citation: Int J Impot Res. 2004 Feb;16(1):95-7
references.pmid: 14963480
references.citation: Nature. 2005 Mar 3;434(7029):113-8
references.pmid: 15744310
references.citation: Exp Physiol. 2003 Jan;88(1):99-107
references.pmid: 12525859
references.citation: Exp Gerontol. 2006 Nov;41(11):1149-56
references.pmid: 17029665
references.citation: Br J Sports Med. 2000 Aug;34(4):273-8
references.pmid: 10953900
references.citation: Mol Hum Reprod. 2002 Aug;8(8):719-21
references.pmid: 12149402
references.citation: Genes Dev. 2008 Jun 1;22(11):1427-38
references.pmid: 18519635
references.citation: Aging (Albany NY). 2009 Sep 12;1(9):818-30
references.pmid: 20157569
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15148-53
references.pmid: 17005726
references.citation: Exp Gerontol. 2013 Sep;48(9):858-68
references.pmid: 23747682
references.citation: Proc Nutr Soc. 2004 May;63(2):293-300
references.pmid: 15294046
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4135-40
references.pmid: 21368114
references.citation: Apoptosis. 2006 Dec;11(12):2115-26
references.pmid: 17051337
references.citation: Am J Physiol Regul Integr Comp Physiol. 2002 Feb;282(2):R519-27
references.pmid: 11792662
references.citation: Am J Clin Nutr. 2009 Jan;89(1):467S-71S
references.pmid: 19056588
references.citation: Antioxid Redox Signal. 2011 Feb 1;14(3):459-68
references.pmid: 20649461
references.citation: Endocr Res. 1984;10(1):27-38
references.pmid: 6745209
references.citation: Annu Rev Genet. 1993;27:437-96
references.pmid: 8122909
references.citation: FASEB J. 2004 Jul;18(10):1150-2
references.pmid: 15132982
references.citation: J Endocrinol. 2008 Nov;199(2):333-41
references.pmid: 18701639