Skip to main content

Advertisement

SpringerLink
Log in

Ovariectomy causes immunosenescence and oxi-inflamm-ageing in peritoneal leukocytes of aged female mice similar to that in aged males

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Immunosenescence involves age-associated restructuring changes of innate and adaptative immune functions. We have suggested that these changes of the immune system participate in the rate of ageing through modulating oxi-inflamm-ageing. Thus, age-related changes in the immune system can be biological age markers and predictors of longevity. Gender differences in oxidation status and immune functions have been observed in rats, with males showing higher oxidation and immunosenescence than females of the same age. Oestrogens are sex hormones that actively participate in modulating the mammalian immune function and, therefore, the age-related impairment of the immune response is drastically accelerated in females during the menopausal transition. Ovariectomy in rodents constitutes a good model for mimicking human oestrogen loss and thus the menopausal situation. Recently, we have shown the deleterious effects of oestrogen loss on several functions of leukocytes from immune organs in rats and mice. In addition, ovariectomised rats show similar levels in these immune functions to those in males. The present work studied several functions as well as inflammatory and oxidative stress parameters in mouse peritoneal macrophages and lymphocytes from old sham and ovariectomised females, as well as in males of the same age. In general, the results show that females, which have a higher immune response and a lower oxidation and inflammation than males, appear similar to males in the parameters studied when they have lost oestrogens by ovariectomy. Thus, these data support the positive role of oestrogens in the immune function through the ageing process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ackerman LS (2006) Sex hormones and the genesis of autoimmunity. Arch Dermatol 142:371–376

    Article  PubMed  CAS  Google Scholar 

  • Alvarado C, Álvarez P, Guayerbas N, Puerto M, Jiménez L, De la Fuente M (2005a) El daño peroxidativo en leucocitos peritoneales de ratones viejos disminuye si se suplementa la dieta con galletas enriquecidas con antioxidantes. Relación con la supervivencia. Rev Esp Geriatr Gerontol 40:351–356

    Article  Google Scholar 

  • Alvarado C, Álvarez P, Jiménez L, De la Fuente M (2005b) Improvement of leukocyte functions in prematurely ageing mice after a 5-week ingestion of a diet supplemented with biscuits enriched in antioxidants. Antiox Redox Signal 7:1203–1210

    Article  CAS  Google Scholar 

  • Alvarado C, Alvarez P, Jimenez L, De la Fuente M (2006) Oxidative stress in leukocytes from young prematurely ageing mice is reversed by supplementation with biscuits rich in antioxidants. Dev Comp Immunol 30:1168–1180

    Article  PubMed  CAS  Google Scholar 

  • Amir SH, Kuhle CL, Fitzpatrick LA (2003) Comprehensive evaluation of the older woman. Mayo Clin Proc 78:1157–1185

    Article  Google Scholar 

  • Arranz L, Caamano JH, Lord JM, De la Fuente M (2010a) Preserved immune functions and controlled leukocyte oxidative stress in naturally long-lived mice: possible role of nuclear factor kappa B. J Gerontol A Biol Sci Med Sci 65:941–950

    Article  PubMed  Google Scholar 

  • Arranz L, De Castro NM, Baeza I, Maté I, Viveros MP, De la Fuente M (2010b) Environmental enrichment improves age-related immune system impairment: long-term exposure since adulthood increases life span in mice. Rej Res 13:415–428

    Article  Google Scholar 

  • Azevedo RB, Lacava ZGM, Miyasaka CK, Chaves SB, Curi R (2001) Regulation of antioxidant enzyme activities in male and female rat macrophages by sex steroids. Braz J Med Biol Res 34:683–687

    Article  PubMed  CAS  Google Scholar 

  • Baeza I, Alvarado C, Alvarez P, Salazar V, Castillo C, Ariznavarreta C, Fdez-Tresguerres J, De la Fuente M (2009) Improvement of leucocyte functions in ovariectomised aged rats after treatment with growth hormone, melatonin, oestrogens or phytoestrogens. J Reprod Immunol 80:70–79

    Article  PubMed  CAS  Google Scholar 

  • Baeza I, De Castro NM, Gimenez-Llort L, De la Fuente M (2010a) Ovariectomy, a model of menopause in rodents, causes a premature ageing of the nervous and immune system. J Neuroimmunol 219:90–99

    Article  PubMed  CAS  Google Scholar 

  • Baeza I, Fdez-Tresguerres J, Ariznavarreta C, De la Fuente M (2010b) Effects of growth hormone, melatonin, oestrogens and phytoestrogens on the oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio and lipid peroxidation in aged ovariectomized rats. Biogerontology 11:687–701

    Article  PubMed  CAS  Google Scholar 

  • Beers RF, Sizer IW (1952) A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem 195:133–140

    PubMed  CAS  Google Scholar 

  • Bilbo SD, Nelson RJ (2001) Sex steroid hormones enhance immune function in male and female Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 280:R207–R213

    PubMed  CAS  Google Scholar 

  • Borras C, Gambini J, Viña J (2007) Mitochondrial oxidant generation is involved in determining why females live longer than males. Front Biosci 12:1008–1013

    Article  PubMed  CAS  Google Scholar 

  • Bouman A, Heineman MJ, Faas MM (2005) Sex hormones and the immune response in humans. Hum Reprod Update 11:411–423

    Article  PubMed  CAS  Google Scholar 

  • Boyden SV (1962) The chemotaxis effect of mixtures of antibody and antigen on polymorphonuclear leukocytes. J Exp Med 115:453–466

    Article  PubMed  CAS  Google Scholar 

  • Cannon JG, St Pierre BA (1997) Gender differences in host defense mechanisms. J Psychiatr Res 31:99–113

    Article  PubMed  CAS  Google Scholar 

  • Chirico S, Smith C, Marchant C, Mitchinson MJ, Halliwell B (1993) Lipid peroxidation in hyperlipemic patients. A study of plasma using an HPLC-based thiobarbituric acid test. Free Radic Res Commun 19:51–57

    Article  PubMed  CAS  Google Scholar 

  • Cid MC, Kleinman HK, Grant DS, Schnaper HW, Fauci AS, Hoffman GS (1994) Estradiol enhances leukocyte binding to tumor necrosis factor-stimulated endothelial cells via an increase in TNF-induced adhesion molecules E-selectin, intercellular adhesion molecule type I and vascular cell adhesion molecule type I. J Clin Invest 93:17–25

    Article  PubMed  CAS  Google Scholar 

  • De la Fuente M (1985) Changes in the macrophage function with ageing. Comp Biochem Physiol A 81:935–938

    Article  Google Scholar 

  • De la Fuente M, Gimenez Llort L (2010) Models of ageing of neuroimmunomodulation: strategies for its improvement. Neuroimmunomodulation 17:213–216

    Article  PubMed  Google Scholar 

  • De la Fuente M, Miquel J (2009) An update of the oxidation-inflammation theory of ageing: the involvement of the immune system in the oxi-inflamm-ageing. Curr Pharm Des 15:3003–3026

    Article  PubMed  Google Scholar 

  • De la Fuente M, Baeza I, Guayerbas N, Puerto M, Castillo C, Salazar V, Ariznavarreta C, Fdez-Tresguerres J (2004a) Changes with ageing in several leukocyte functions of male and female rats. Biogerontology 5:389–400

    Article  PubMed  Google Scholar 

  • De la Fuente M, Hernanz A, Guayerbas N, Alvarez P, Alvarado C (2004b) Changes with age in peritoneal macrophage functions. Implication of leukocytes in the oxidative stress of senescence. Cell Mol Biol 50(Suppl):OL683–OL690

    PubMed  Google Scholar 

  • Dubal DB, Shughrue PJ, Wilson ME, Merchenthaler I, Wise PM (1999) Estradiol modulates Bcl-2 in cerebral isquemia: a potential role for oestrogen receptors. J Neurosci 19:6385–6393

    PubMed  CAS  Google Scholar 

  • Farage MA, Neill S, MacLean AB (2009) Physiological changes associated with the menstrual cycle: a review. Obstet Gynecol Surv 64:58–72

    Article  PubMed  Google Scholar 

  • Franceschi C, Bonafé M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-ageing. An evolutionary perspective on immunosenescence. Ann NY Acad Sci 908:244–254

    Article  PubMed  CAS  Google Scholar 

  • Gameiro C, Romao F (2010) Changes in the immune system during menopause and ageing. Front Biosci (Elite Ed) 2:1299–1303

    Article  Google Scholar 

  • Guayerbas N, De la Fuente M (2003) An impairment of phagocytic function is linked to a shorter life span in two strains of prematurely ageing mice. Dev Comp Immunol 27:339–350

    Article  PubMed  CAS  Google Scholar 

  • Guayerbas N, Puerto M, Alvarez P, De la Fuente M (2004) Improvement of the macrophage functions in prematurely ageing mice by a diet supplemented with thiolic antioxidants. Cell Mol Biol 50:OL677–OL681

    PubMed  CAS  Google Scholar 

  • Ha BJ, Lee SH, Kim HJ, Lee JY (2006) The role of Salicornia herbacea in ovariectomy-induced oxidative stress. Biol Pharm Bull 29:1305–1309

    Article  PubMed  CAS  Google Scholar 

  • Huber J, Gruver C (2001) Immunological and dermatological impact of progesterone. Gynecol Endocrinol 6:18–21

    Google Scholar 

  • Islander U, Erlandsson MC, Hasseus B, Jonsson CA, Ohlsson C, Gustafsson JA (2003) Influence of oestrogen receptor α and β on the immune system in aged female mice. Immunology 110:149–157

    Article  PubMed  CAS  Google Scholar 

  • Kankofer M, Radzki RP, Bienko M, Albera E (2007) Anti-oxidative/oxidative status of rat liver after ovariectomy. J Vet Med 54:225–229

    Article  CAS  Google Scholar 

  • Keller ET, Zhang J, Yao Z, Qi Y (2001) The impact of chronic oestrogen deprivation on immunologic parameters in the ovariectomised rhesus monkey (Macaca mulatta) model of menopause. J Reprod Immunol 50:41–55

    Article  PubMed  CAS  Google Scholar 

  • Kiray M, Uysal N, Sönmez A, Acikgöt O, Gönenc S (2004) Positive effects of deprenyl and estradiol on spatial memory and oxidant stress in aged female rat brains. Neurosci Lett 354:225–228

    Article  PubMed  CAS  Google Scholar 

  • Kiray M, Ergur BU, Bagriyanik A, Pekcetin C, Aksu I, Buldan Z (2007) Suppression of apoptosis and oxidative stress by deprenyl and estradiol in aged rat liver. Acta Histochem 109:480–485

    Article  PubMed  CAS  Google Scholar 

  • Kireev R, Tresguerres AF, Vara E, Ariznavarreta C, Tresguerres JA (2007) Effect of chronic treatments with GH, melatonin, oestrogens, and phyto-oestrogens on oxidative stress parameters in liver from aged female rats. Biogerontology 8:469–482

    Article  PubMed  CAS  Google Scholar 

  • Kovacs EJ (2005) Ageing, traumatic injury and oestrogen treatment. Exp Gerontol 40:549–555

    Article  PubMed  CAS  Google Scholar 

  • Lawrence RA, Burck RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952–958

    Article  PubMed  CAS  Google Scholar 

  • Lu KH, Hopper BR, Vargo TM, Yen SS (1979) Chronological changes in sex steroids gonadotropin and prolactin secretion in ageing female rats displaying different reproductive states. Biol Reprod 21:193–203

    Article  PubMed  CAS  Google Scholar 

  • Marriott I, Huet-Hudson YM (2006) Sexual dimorphism in innate immune responses to infectious organisms. Immunol Res 34:177–192

    Article  PubMed  CAS  Google Scholar 

  • Massafra C, Gioia D, De Felice C, Picciolini E, De Leo V, Bonifazi M, Bernabei A (2000) Effects of oestrogens and androgens on erythrocyte antioxidant superoxide dismutase, catalase and glutathione peroxidase activities during the menstrual cycle. J Endocrinol 167:447–452

    Article  PubMed  CAS  Google Scholar 

  • Miquel J, Ramírez-Boscá A, Ramírez-Boscá JV, Alperi JD (2006) Menopause: a review on the role of oxygen stress and favorable effects of dietary antioxidants. Arch Gerontol Geriatr 42:289–306

    Article  PubMed  CAS  Google Scholar 

  • Nelson HD (2008) Menopause. Lancet 371:760–770

    Article  PubMed  Google Scholar 

  • Nunn CL, Lindenfors P, Pursall ER, Rolff J (2009) On sexual dimorphism in immune function. Philos Trans R Soc B 364:61–69

    Article  Google Scholar 

  • Pauklin S, Petersen-Mahrtz SK (2009) Progesterone inhibits activation-induced deaminase by binding to the promoter. J Immunol 183:1238–1244

    Article  PubMed  CAS  Google Scholar 

  • Pfeilschifter J, Köditz R, Pfohl M, Schatz H (2002) Changes in proinflammatory cytokine activity after menopause. Endocr Rev 23:90–119

    Article  PubMed  CAS  Google Scholar 

  • Porter VR, Greendale GA, Schocken M, Zhu X, Effros RB (2001) Immune effects of hormone replacement therapy in post-menopausal women. Exp Gerontol 36:311–326

    Article  PubMed  CAS  Google Scholar 

  • Sebastián C, Espia M, Serra M, Celada A, Lloberas J (2005) MacrophAgeing: a cellular and molecular review. Immunobiology 210:121–126

    Article  PubMed  Google Scholar 

  • Sies H (1999) Glutathione and its role in cellular functions. Free Radic Biol Med 27:916–921

    Article  PubMed  CAS  Google Scholar 

  • Tietze F (1969) Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione. Anal Biochem 17:502–522

    Article  Google Scholar 

  • Tresguerres JAF, Kireev R, Tresguerres AF, Borrás C, Vara E, Ariznavarreta C (2008) Molecular mechanisms involved in the hormonal prevention of ageing in the rat. J Ster Biochem Mol Biol 108:318–326

    Article  CAS  Google Scholar 

  • Viña J, Borrás C, Gambini J, Sastre J, Pallardó FV (2005) Why females live longer than males: control of longevity by sex hormones. Sci Ageing Knowledge Environ 23:pe17

    Article  Google Scholar 

  • Viña J, Sastre J, Pallardó FV, Gambini J, Borrás C (2006) Role of mitochondrial oxidative stress to explain the different longevity between genders: protective effect of oestrogens. Free Radic Res 40:1359–1365

    Article  PubMed  Google Scholar 

  • Viña J, Sastre J, Pallardó FV, Gambini J, Borrás C (2008) Modulation of longevity-associated genes by oestrogens or phyto-oestrogens. Biol Chem 389:273–277

    Article  PubMed  Google Scholar 

  • Wayne SJ, Rhyne RL, Garry PJ, Goodwin JS (1990) Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60. J Gerontol 45:45–98

    Google Scholar 

  • Wirleitner B, Baier-Bitterlich G, Bock G, Widner B, Fuchs D (1998) 7,8-Dihydroneopterin-induced apoptosis in Jurkat T lymphocytes: a comparison with anti-Fas- and hydrogen peroxide-mediated cell death. Biochem Pharmacol 56:1181–1187

    Article  PubMed  CAS  Google Scholar 

  • Yalin S, Comelekoglu U, Bagis S, Sahin NO, Ogenler O, Hatungil R (2006) Acute effect of single-dose cadmium treatment on lipid peroxidation and antioxidant enzymes in ovariectomised rats. Ecotoxicol Environ Saf 65:140–144

    Article  PubMed  CAS  Google Scholar 

  • Yang JH, Chen CD, Wu MY, Chao KH, Yang YS, Ho HN (2000) Hormone replacement therapy reverses the decrease in natural killer cytotoxicity but does not reverse the decreases in the T-cell subpopulation of interferon-gamma production in postmenopausal women. Feril Steril 74:261–267

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by MICINN (BFU2008-04336); Complutense University Research Group (910379) and RETICEF (RD06/0013/0002 and RD06/0013/0003) from ISCIII.

Conflict of interest

The authors state that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Physiology, Faculty of Biology, Complutense University of Madrid (UCM), c/Jose Antonio Novais no. 2, 28040, Madrid, Spain

    Isabel Baeza, Nuria M. De Castro, Lorena Arranz & Mónica De la Fuente

  2. Department of Physiology, Faculty of Medicine, Complutense University of Madrid, 28040, Madrid, Spain

    Jesús Fdez-Tresguerres

Authors
  1. Isabel Baeza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nuria M. De Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lorena Arranz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jesús Fdez-Tresguerres
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mónica De la Fuente
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mónica De la Fuente.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baeza, I., De Castro, N.M., Arranz, L. et al. Ovariectomy causes immunosenescence and oxi-inflamm-ageing in peritoneal leukocytes of aged female mice similar to that in aged males. Biogerontology 12, 227–238 (2011). https://doi.org/10.1007/s10522-010-9317-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-010-9317-0

Keywords

Search

Navigation