Search for other papers by Driele N. Garcia in
Current site
Google Scholar
PubMed
Search for other papers by Jéssica D. Hense in
Current site
Google Scholar
PubMed
Search for other papers by Bianka M. Zanini in
Current site
Google Scholar
PubMed
Search for other papers by José V. V. Isola in
Current site
Google Scholar
PubMed
Search for other papers by Jorgea Pradiee in
Current site
Google Scholar
PubMed
Search for other papers by Juliane B. Prosczek in
Current site
Google Scholar
PubMed
Search for other papers by Joao A. Alvarado-Rincón in
Current site
Google Scholar
PubMed
Search for other papers by Rafael G. Mondadori in
Current site
Google Scholar
PubMed
Search for other papers by Jeffrey B. Mason in
Current site
Google Scholar
PubMed
Search for other papers by Miguel A. Brieño-Enríquez in
Current site
Google Scholar
PubMed
Search for other papers by Carlos C. Barros in
Current site
Google Scholar
PubMed
Search for other papers by Michael B. Stout in
Current site
Google Scholar
PubMed
Department of Head and Neck Surgery, Poznan University of Medical Sciences,
Search for other papers by Michal M. Masternak in
Current site
Google Scholar
PubMed
Search for other papers by Augusto Schneider in
Current site
Google Scholar
PubMed
Abstract
Cellular senescence is a defense mechanism to arrest proliferation of damaged cells. The number of senescent cells increases with age in different tissues and contributes to the development of age-related diseases. Old mice treated with senolytics drugs, dasatinib and quercetin (D+Q), have reduced senescent cells burden. The aim of this study was to evaluate the effects of D+Q on testicular function and fertility of male mice. Mice (n = 9/group) received D (5 mg kg−1) and Q (50 mg kg−1) via gavage every moth for three consecutive days from 3 to 8 months of age. At 8 months mice were breed with young non-treated females and euthanized. The treatment of male mice with D+Q increased serum testosterone levels and sperm concentration and decreased abnormal sperm morphology. Sperm motility, seminiferous tubule morphometry, testicular gene expression and fertility were not affected by treatment. There was no effect of D+Q treatment in β-galactosidase activity and in lipofuscin staining in testes. D+Q treatment also did not affect body mass gain and testes mass. In conclusion, D+Q treatment increased serum testosterone levels and sperm concentration and decreased abnormal sperm morphology, however did not affect fertility. Further studies with older mice and different senolytics are necessary to elucidate the effects in the decline of sperm output (quality and quantity) associated with aging.
Supplementary Materials
- Supplemental Material
-
1.
Gems D, Kern CC. Is “cellular senescence” a misnomer? Geroscience 2022; 44(5): 2461–2469. https://doi.org/10.1007/s11357-022-00652-x.
-
2.
Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 2013; 123(3): 966–972. https://doi.org/10.1172/JCI64098.
-
3.
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013; 153(6): 1194–1217. https://doi.org/10.1016/j.cell.2013.05.039.
-
4.
Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, et al. Cellular senescence: defining a path forward. Cell 2019; 179(4): 813–827. https://doi.org/10.1016/j.cell.2019.10.005.
-
5.
Mylonas A, O'Loghlen A. Cellular senescence and ageing: mechanisms and interventions. Front Aging 2022; 3: 866718. https://doi.org/10.3389/fragi.2022.866718.
-
6.
Xu M, Pirtskhalava T, Farr JN, Weigand BM, Palmer AK, Weivoda MM, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med 2018; 24(8): 1246–1256. https://doi.org/10.1038/s41591-018-0092-9.
-
7.
Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 2015; 14(4): 644–658. https://doi.org/10.1111/acel.12344.
-
8.
Justice JN, Nambiar AM, Tchkonia T, LeBrasseur NK, Pascual R, Hashmi SK, et al. Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study. EBioMedicine 2019; 40: 554–563. https://doi.org/10.1016/j.ebiom.2018.12.052.
-
9.
Hense JD, Garcia DN, Isola JV, Alvarado-Rincon JA, Zanini BM, Prosczek JB, et al. Senolytic treatment reverses obesity-mediated senescent cell accumulation in the ovary. Geroscience 2022; 44(3): 1747–1759. https://doi.org/10.1007/s11357-022-00573-9.
-
10.
Harris ID, Fronczak C, Roth L, Meacham RB. Fertility and the aging male. Rev Urol 2011; 13(4): e184–e190.
-
11.
Oliveira JBA, Petersen CG, Mauri AL, Vagnini LD, Baruffi RLR, Franco JG Jr. The effects of age on sperm quality: an evaluation of 1,500 semen samples. JBRA Assist Reprod 2014; 18(2): 34–41. https://doi.org/10.5935/1518-0557.20140002.
-
12.
Smith LB, Walker WH. The regulation of spermatogenesis by androgens. Semin Cell Dev Biol 2014; 30: 2–13. https://doi.org/10.1016/j.semcdb.2014.02.012.
-
13.
Kenyon CJ. The genetics of ageing. Nature 2010; 464(7288): 504–512. https://doi.org/10.1038/nature08980.
-
14.
Garcia DN, Saccon TD, Pradiee J, Rincon JAA, Andrade KRS, Rovani MT, et al. Effect of caloric restriction and rapamycin on ovarian aging in mice. Geroscience 2019; 41(4): 395–408. https://doi.org/10.1007/s11357-019-00087-x.
-
15.
Chen H, Luo L, Liu J, Brown T, Zirkin BR. Aging and caloric restriction: effects on Leydig cell steroidogenesis. Exp Gerontol 2005; 40(6): 498–505. https://doi.org/10.1016/j.exger.2005.03.011.
-
16.
Sitzmann BD, Leone EH, Mattison JA, Ingram DK, Roth GS, Urbanski HF, et al. Effects of moderate calorie restriction on testosterone production and semen characteristics in young rhesus macaques (Macaca mulatta). Biol Reprod 2010; 83(4): 635–640. https://doi.org/10.1095/biolreprod.110.084186.
-
17.
Martins AD, Jarak I, Morais T, Carvalho RA, Oliveira PF, Monteiro MP, et al. Caloric restriction alters the hormonal profile and testicular metabolome, resulting in alterations of sperm head morphology. Am J Physiol Endocrinol Metab 2020; 318(1): E33–E43. https://doi.org/10.1152/ajpendo.00355.2019.
-
18.
Bitto A, Ito TK, Pineda VV, LeTexier NJ, Huang HZ, Sutlief E, et al. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. Elife 2016; 5: e16351. https://doi.org/10.7554/eLife.16351.
-
19.
Jesus TT, Oliveira PF, Sousa M, Cheng CY, Alves MG. Mammalian target of rapamycin (mTOR): a central regulator of male fertility? Crit Rev Biochem Mol Biol 2017; 52(3): 235–253. https://doi.org/10.1080/10409238.2017.1279120.
-
20.
Khaki A, Fathiazad F, Nouri M, Khaki A, Maleki NA, Khamnei HJ, et al. Beneficial effects of quercetin on sperm parameters in streptozotocin-induced diabetic male rats. Phytother Res 2010; 24(9): 1285–1291. https://doi.org/10.1002/ptr.3100.
-
21.
Ramu S, Jeyendran RS. The hypo-osmotic swelling test for evaluation of sperm membrane integrity. Methods Mol Biol 2013; 927: 21–25. https://doi.org/10.1007/978-1-62703-038-0_3.
-
22.
Agarwal A, Gupta S, Sharma R. Hypoosmotic swelling test (HOS). In: Andrological evaluation of male infertility. Springer International Publishing 2016; 93–96. https://doi.org/10.1007/978-3-319-26797-5_12.
-
23.
Wu Y, Zhong A, Zheng H, Jiang M, Xia Z, Yu J, et al. Expression of flotilin-2 and acrosome biogenesis are regulated by MiR-124 during spermatogenesis. PLoS One 2015; 10(8): e0136671. https://doi.org/10.1371/journal.pone.0136671.
-
24.
Isola JVV, Veiga GB, de Brito CRC, Alvarado-Rincon JA, Garcia DN, Zanini BM, et al. 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs. Geroscience 2022. https://doi.org/10.1007/s11357-022-00601-8.
-
25.
Snyder AN, Crane JS. Histology, lipofuscin. [Internet]. Treasure Island, FL: StatPearls Publishing; 2019. [updated 2022 May 8; cited 2023 Jan 25]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK537358/.
-
26.
Evangelou K, Gorgoulis VG. Sudan Black B, the specific histochemical stain for lipofuscin: a novel method to detect senescent cells. Methods Mol Biol 2017; 1534: 111–119. https://doi.org/10.1007/978-1-4939-6670-7_10.
-
27.
Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 2002; 3(7): research0034. https://doi.org/10.1186/gb-2002-3-7-research0034.
-
28.
Fuhrmann-Stroissnigg H, Santiago FE, Grassi D, Ling YY, Niedernhofer LJ, Robbins PD. SA-β-galactosidase-based screening assay for the identification of senotherapeutic drugs. J Vis Exp 2019; 148: e58133. https://doi.org/10.3791/58133.
-
29.
Cai Y, Zhou H, Zhu Y, Sun Q, Ji Y, Xue A, et al. Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice. Cell Res 2020; 30(7): 574–589. https://doi.org/10.1038/s41422-020-0314-9.
-
30.
Dungan CM, Murach KA, Zdunek CJ, Tang ZJ, VonLehmden GL, Brightwell CR, et al. Deletion of SA β‐Gal+ cells using senolytics improves muscle regeneration in old mice. Aging Cell 2022; 21(1): e13528. https://doi.org/10.1111/acel.13528.
-
31.
Cheng CY, Mruk DD. The blood-testis barrier and its implications for male contraception. Pharmacol Rev 2012; 64(1): 16–64. https://doi.org/10.1124/pr.110.002790.
-
32.
Yule TD, Mahi-Brown CA, Tung KS. Role of testicular autoantigens and influence of lymphokines in testicular autoimmune disease. J Reprod Immunol 1990; 18(1): 89–103. https://doi.org/10.1016/0165-0378(90)90026-3.
-
33.
Georgakopoulou EA, Tsimaratou K, Evangelou K, Fernandez Marcos PJ, Zoumpourlis V, Trougakos IP, et al. Specific lipofuscin staining as a novel biomarker to detect replicative and stress-induced senescence. A method applicable in cryo-preserved and archival tissues. Aging (Albany NY) 2013; 5(1): 37–50. https://doi.org/10.18632/aging.100527.
-
34.
Nistal M, González-Peramato P, Serrano Á. Testicular changes in Elderly men. In: Clues in the diagnosis of non-tumoral testicular pathology. Cham: Springer International Publishing 2017; 349–361. https://doi.org/10.1007/978-3-319-49364-0_39.
-
35.
Ansere VA, Ali-Mondal S, Sathiaseelan R, Garcia DN, Isola JVV, Henseb JD, et al. Cellular hallmarks of aging emerge in the ovary prior to primordial follicle depletion. Mech Ageing Dev 2021; 194: 111425. https://doi.org/10.1016/j.mad.2020.111425.
-
36.
Hudgins AD, Tazearslan C, Tare A, Zhu Y, Huffman D, Suh Y. Age- and tissue-specific expression of senescence biomarkers in mice. Front Genet 2018; 9: 59. https://doi.org/10.3389/fgene.2018.00059.
-
37.
Martin LJ, Touaibia M. Improvement of testicular steroidogenesis using flavonoids and isoflavonoids for prevention of late-onset male hypogonadism. Antioxidants (Basel) 2020; 9(3): 237. https://doi.org/10.3390/antiox9030237.
-
38.
Holdcraft RW, Braun RE. Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development 2004; 131(2): 459–467. https://doi.org/10.1242/dev.00957.
-
39.
Katragadda V, Adem M, Mohammad RA, Sri Bhasyam S, Battini K. Testosterone recuperates deteriorated male fertility in cypermethrin intoxicated rats. Toxicol Res 2021; 37(1): 125–134. https://doi.org/10.1007/s43188-020-00046-1.
-
40.
Gilbert SF. Developmental biology, 6th ed. Sunderland, Mass., Bethesda, MD, USA: Sinauer Associates; 2000. Available at: https://www.ncbi.nlm.nih.gov/books/NBK9983/.
-
41.
Ozkosem B, Feinstein SI, Fisher AB, O'Flaherty C. Advancing age increases sperm chromatin damage and impairs fertility in peroxiredoxin 6 null mice. Redox Biol 2015; 5: 15–23. https://doi.org/10.1016/j.redox.2015.02.004.
-
42.
Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: a bioactive flavonoid. Pharmacogn Rev 2016; 10(20): 84–89. https://doi.org/10.4103/0973-7847.194044.
-
43.
Desai N, Sabanegh E Jr., Kim T, Agarwal A. Free radical theory of aging: implications in male infertility. Urology 2010; 75(1): 14–19. https://doi.org/10.1016/j.urology.2009.05.025.
-
44.
Ranawat P, Kaushik G, Saikia UN, Pathak CM, Khanduja KL. Quercetin impairs the reproductive potential of male mice. Andrologia 2013; 45(1): 56–65. https://doi.org/10.1111/j.1439-0272.2012.01311.x.
-
45.
Caocci G, Atzeni S, Orru N, Azzena L, Martorana L, Littera R, et al. Gynecomastia in a male after dasatinib treatment for chronic myeloid leukemia. Leukemia 2008; 22(11): 2127–2128. https://doi.org/10.1038/leu.2008.106.
Editor-in-Chief
László ROSIVALL (Semmelweis University, Budapest, Hungary)
Managing Editor
Anna BERHIDI (Semmelweis University, Budapest, Hungary)
Co-Editors
- Gábor SZÉNÁSI (Semmelweis University, Budapest, Hungary)
- Ákos KOLLER (Semmelweis University, Budapest, Hungary)
- Zsolt RADÁK (University of Physical Education, Budapest, Hungary)
- László LÉNÁRD (University of Pécs, Hungary)
- Zoltán UNGVÁRI (Semmelweis University, Budapest, Hungary)
Assistant Editors
- Gabriella DÖRNYEI (Semmelweis University, Budapest, Hungary)
- Zsuzsanna MIKLÓS (Semmelweis University, Budapest, Hungary)
- György NÁDASY (Semmelweis University, Budapest, Hungary)
Hungarian Editorial Board
- György BENEDEK (University of Szeged, Hungary)
- Zoltán BENYÓ (Semmelweis University, Budapest, Hungary)
- Mihály BOROS (University of Szeged, Hungary)
- László CSERNOCH (University of Debrecen, Hungary)
- Magdolna DANK (Semmelweis University, Budapest, Hungary)
- László DÉTÁRI (Eötvös Loránd University, Budapest, Hungary)
- Zoltán GIRICZ (Semmelweis University, Budapest, Hungary and Pharmahungary Group, Szeged, Hungary)
- Zoltán HANTOS (Semmelweis University, Budapest and University of Szeged, Hungary)
- Zoltán HEROLD (Semmelweis University, Budapest, Hungary)
- László HUNYADI (Semmelweis University, Budapest, Hungary)
- Gábor JANCSÓ (University of Pécs, Hungary)
- Zoltán KARÁDI (University of Pecs, Hungary)
- Miklós PALKOVITS (Semmelweis University, Budapest, Hungary)
- Gyula PAPP (University of Szeged, Hungary)
- Gábor PAVLIK (University of Physical Education, Budapest, Hungary)
- András SPÄT (Semmelweis University, Budapest, Hungary)
- Gyula SZABÓ (University of Szeged, Hungary)
- Zoltán SZELÉNYI (University of Pécs, Hungary)
- Lajos SZOLLÁR (Semmelweis University, Budapest, Hungary)
- József TOLDI (MTA-SZTE Neuroscience Research Group and University of Szeged, Hungary)
- Árpád TÓSAKI (University of Debrecen, Hungary)
International Editorial Board
- Dragan DJURIC (University of Belgrade, Serbia)
- Christopher H. FRY (University of Bristol, UK)
- Stephen E. GREENWALD (Blizard Institute, Barts and Queen Mary University of London, UK)
- Tibor HORTOBÁGYI (University of Groningen, Netherlands)
- George KUNOS (National Institutes of Health, Bethesda, USA)
- Massoud MAHMOUDIAN (Iran University of Medical Sciences, Tehran, Iran)
- Tadaaki MANO (Gifu University of Medical Science, Japan)
- Luis Gabriel NAVAR (Tulane University School of Medicine, New Orleans, USA)
- Hitoo NISHINO (Nagoya City University, Japan)
- Ole H. PETERSEN (Cardiff University, UK)
- Ulrich POHL (German Centre for Cardiovascular Research and Ludwig-Maximilians-University, Planegg, Germany)
- Andrej A. ROMANOVSKY (University of Arizona, USA)
- Anwar Ali SIDDIQUI (Aga Khan University, Karachi, Pakistan)
- Csaba SZABÓ (University of Fribourg, Switzerland)
- Eric VICAUT (Université de Paris, UMRS 942 INSERM, France)
Editorial Correspondence:
Physiology International
Semmelweis University
Faculty of Medicine, Institute of Translational Medicine
Nagyvárad tér 4, H-1089 Budapest, Hungary
Phone/Fax: +36-1-2100-100
E-mail: pi@semmelweis.hu
Indexing and Abstracting Services:
- Biological Abstracts
- BIOSIS Previews
- CAB Abstracts
- CABELLS Journalytics
- EMBASE/Excerpta Medica
- Global Health
- Index Copernicus
- Index Medicus
- Medline
- Referativnyi Zhurnal
- SCOPUS
- WoS - Science Citation Index Expanded
| 2023 | |
|---|---|
| Web of Science | |
| Journal Impact Factor | 2.2 |
| Rank by Impact Factor | Q3 (Physiology) |
| Journal Citation Indicator | 0.58 |
| Scopus | |
| CiteScore | 3.4 |
| CiteScore rank | Q2 (Physical Therapy, Sports Therapy and Rehabilitation) |
| SNIP | 0.508 |
| Scimago | |
| SJR index | 0.407 |
| SJR Q rank | Q2 |
| Physiology International | |
|---|---|
| Publication Model | Hybrid |
| Submission Fee | none |
| Article Processing Charge | 1100 EUR/article |
| Printed Color Illustrations | 40 EUR (or 10 000 HUF) + VAT / piece |
| Regional discounts on country of the funding agency | World Bank Lower-middle-income economies: 50% World Bank Low-income economies: 100% |
| Further Discounts | Editorial Board / Advisory Board members: 50% Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100% |
| Subscription fee 2025 | Online subsscription: 752 EUR / 828 USD Print + online subscription: 880 EUR / 968 USD |
| Subscription Information | Online subscribers are entitled access to all back issues published by Akadémiai Kiadó for each title for the duration of the subscription, as well as Online First content for the subscribed content. |
| Purchase per Title | Individual articles are sold on the displayed price. |
| Physiology International | |
|---|---|
| Language | English |
| Size | B5 |
| Year of Foundation |
2006 (1950) |
| Volumes per Year |
1 |
| Issues per Year |
4 |
| Founder | Magyar Tudományos Akadémia |
| Founder's Address |
H-1051 Budapest, Hungary, Széchenyi István tér 9. |
| Publisher | Akadémiai Kiadó |
| Publisher's Address |
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245. |
| Responsible Publisher |
Chief Executive Officer, Akadémiai Kiadó |
| ISSN | 2498-602X (Print) |
| ISSN | 2677-0164 (Online) |
Monthly Content Usage
| Abstract Views | Full Text Views | PDF Downloads | |
|---|---|---|---|
| Apr 2024 | 227 | 2 | 2 |
| May 2024 | 342 | 2 | 5 |
| Jun 2024 | 302 | 0 | 0 |
| Jul 2024 | 225 | 0 | 0 |
| Aug 2024 | 186 | 0 | 0 |
| Sep 2024 | 126 | 0 | 0 |
| Oct 2024 | 94 | 1 | 1 |
Copyright Akadémiai Kiadó AKJournals is the trademark of Akadémiai Kiadó's journal publishing business branch.