Skip to main content

Advertisement

Log in

Sex- and age-specific differences in core body temperature of C57Bl/6 mice

  • Published:
AGE Aims and scope Submit manuscript

Abstract

Gender-specific differences in longevity are reported across species and are mediated by mechanisms not entirely understood. In C57Bl/6 mice, commonly used in aging research, males typically outlive females. Since in these animals modest but prolonged reduction of core body (Tc) increased life span, we hypothesized that differential Tc may contribute to sex-specific longevity. Here, we compared the circadian profiles of Tc and locomotor activity (LMA) of male and female C57Bl/6 mice. Since Tc and LMA normally change with age, measurements were carried out in young (3 months) as well as in old (24 months) mice. In young females, Tc was influenced by estrous but was overall higher than in males. This difference was larger in old animals after age eliminated the variations associated with estrous. Although temperature homeostasis is regulated centrally by the sexually dimorphic hypothalamic preoptic area, these differences were uniquely dependent on the gonads. In fact, bilateral gonadectomy abolished the effects of estrous and increased resting Tc in males eliminating all sex-specific differences in Tc and LMA. These effects were only partially mimicked by hormonal replacement as Tc was affected by progesterone and to a lesser extent by estrogen but not by testosterone. Thus, gonadal-dependent modulation of Tc may be one of the physiological parameters contributing to gender-specific differences in longevity.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abe J, Okazawa M et al (2003) Primary cold-sensitive neurons in acutely dissociated cells of rat hypothalamus. Neurosci Lett 342(1–2):29–32

    Article  CAS  PubMed  Google Scholar 

  • Ali SS, Xiong C et al (2006) Gender differences in free radical homeostasis during aging: shorter-lived female C57BL6 mice have increased oxidative stress. Aging Cell 5(6):565–574

    Article  CAS  PubMed  Google Scholar 

  • Boulant JA (2006) Neuronal basis of Hammel's model for set-point thermoregulation. J Appl Physiol 100(4):1347–1354

    Article  PubMed  Google Scholar 

  • Brown RE, Gander GW et al (1970) Estrogen and cortisone: effects on thermoregulation in the female rabbit. Proc Soc Exp Biol Med 134(1):83–86

    CAS  PubMed  Google Scholar 

  • Brown-Borg HM, Borg KE et al (1996) Dwarf mice and the ageing process. Nature 384(6604):33

    Article  CAS  PubMed  Google Scholar 

  • Carandente F, De Matteis MA et al (1982) Circadian temperature rhythm in intact, sham operated, gonadectomized rats. Chronobiologia 9(2):211–221

    CAS  PubMed  Google Scholar 

  • Cargill SL, Carey JR et al (2003) Age of ovary determines remaining life expectancy in old ovariectomized mice. Aging Cell 2(3):185–190

    Article  CAS  PubMed  Google Scholar 

  • Conti B, Sugama S et al (2000) Modulation of IL-18 production in the adrenal cortex following acute ACTH or chronic corticosterone treatment. Neuroimmunomodulation 8(1):1–7

    Article  CAS  PubMed  Google Scholar 

  • Conti B, Sanchez-Alavez M et al (2006) Transgenic mice with a reduced core body temperature have an increased life span. Science 314(5800):825–828

    Article  CAS  PubMed  Google Scholar 

  • Coomber P, Crews D et al (1997) Independent effects of incubation temperature and gonadal sex on the volume and metabolic capacity of brain nuclei in the leopard gecko (Eublepharis macularius), a lizard with temperature-dependent sex determination. J Comp Neurol 380(3):409–421

    Article  CAS  PubMed  Google Scholar 

  • Coschigano KT, Clemmons D et al (2000) Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 141(7):2608–2613

    Article  CAS  PubMed  Google Scholar 

  • Coschigano KT, Holland AN et al (2003) Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology 144(9):3799–3810

    Article  CAS  PubMed  Google Scholar 

  • Crews D, Coomber P et al (1996) Brain organization in a reptile lacking sex chromosomes: effects of gonadectomy and exogenous testosterone. Horm Behav 30(4):474–486

    Article  CAS  PubMed  Google Scholar 

  • Dalal SJ, Estep JS et al (2001) Standardization of the Whitten effect to induce susceptibility to Neisseria gonorrhoeae in female mice. Contemp Top Lab Anim Sci 40(2):13–17

    CAS  PubMed  Google Scholar 

  • Drori D, Folman Y (1986) Interactive environmental and genetic effects on longevity in the male rat: litter size, exercise, electric shocks and castration. Exp Aging Res 12(2):59–64

    CAS  PubMed  Google Scholar 

  • Flurkey K, Papaconstantinou J et al (2001) Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci USA 98(12):6736–6741

    Article  CAS  PubMed  Google Scholar 

  • Flurkey K, Papaconstantinou J et al (2002) The Snell dwarf mutation Pit1(dw) can increase life span in mice. Mech Ageing Dev 123(2–3):121–130

    Article  CAS  PubMed  Google Scholar 

  • Fregly MJ, Kelleher DL et al (1979) Tolerance of estrogen-treated rats to acute cold exposure. J Appl Physiol 47(1):59–66

    CAS  PubMed  Google Scholar 

  • Gangwar PC (1982) Effects of climate on the thermoregulatory responses of male buffalo (Bubalus-bubalis) Calves supplemented with different levels of testosterone and TDN. Int J Biometeorol 26(1):73–79

    Article  CAS  PubMed  Google Scholar 

  • Goldman JM, Murr AS et al (2007) The rodent estrous cycle: characterization of vaginal cytology and its utility in toxicological studies. Birth Defects Res B Dev Reprod Toxicol 80(2):84–97

    Article  CAS  PubMed  Google Scholar 

  • Gordon CJ (1993) Temperature regulation in laboratory rodents. Cambridge University Press, New York

    Book  Google Scholar 

  • Gordon CJ (2008) Cardiac and thermal homeostasis in the aging Brown Norway rat. J Gerontol A Biol Sci Med Sci 63(12):1307–1313

    PubMed  Google Scholar 

  • Griffin JD, Saper CB et al (2001) Synaptic and morphological characteristics of temperature-sensitive and -insensitive rat hypothalamic neurones. J Physiol 537(Pt 2):521–535

    Article  CAS  PubMed  Google Scholar 

  • Hammel H (1965) Neurons and temperature regulation. In: Yamamoto WS, Brobeck JR (eds) Physiological controls and regulations. Saunders, Philadelphia, pp 71–97

    Google Scholar 

  • Holzenberger M, Dupont J et al (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421(6919):182–187

    Article  CAS  PubMed  Google Scholar 

  • Hori A, Minato K et al (1999) Warming-activated channels of warm-sensitive neurons in rat hypothalamic slices. Neurosci Lett 275(2):93–96

    Article  CAS  PubMed  Google Scholar 

  • Kruijver FP, Swaab DF (2002) Sex hormone receptors are present in the human suprachiasmatic nucleus. Neuroendocrinology 75(5):296–305

    Article  CAS  PubMed  Google Scholar 

  • Kurosu H, Yamamoto M et al (2005) Suppression of aging in mice by the hormone Klotho. Science 309(5742):1829–1833

    Article  CAS  PubMed  Google Scholar 

  • Ladiges W, Van Remmen H et al (2009) Lifespan extension in genetically modified mice. Aging Cell 8(4):346–352

    Article  CAS  PubMed  Google Scholar 

  • Liu RK, Walford RL (1966) Increased growth and life-span with lowered ambient temperature in the annual fish, Cynolebias adloffi. Nature 212:1277–1278

    Article  Google Scholar 

  • Marrone BL, Gentry RT et al (1976) Gonadal hormones and body temperature in rats: effects of estrous cycles, castration and steroid replacement. Physiol Behav 17(3):419–425

    Article  CAS  PubMed  Google Scholar 

  • Mason JB, Cargill SL et al (2009) Transplantation of young ovaries to old mice increased life span in transplant recipients. J Gerontol A Biol Sci Med Sci 64(12):1207–1211

    PubMed  Google Scholar 

  • Mobbs CV, Gee DM et al (1984) Reproductive senescence in female C57BL/6J mice: ovarian impairments and neuroendocrine impairments that are partially reversible and delayable by ovariectomy. Endocrinology 115(5):1653–1662

    Article  CAS  PubMed  Google Scholar 

  • Morrison SF, Nakamura K et al (2008) Central control of thermogenesis in mammals. Exp Physiol 93(7):773–797

    Article  PubMed  Google Scholar 

  • Nakamura K, Morrison SF (2008) A thermosensory pathway that controls body temperature. Nat Neurosci 11(1):62–71

    Article  CAS  PubMed  Google Scholar 

  • Nieschlag E, Nieschlag S et al (1993) Lifespan and testosterone. Nature 366(6452):215

    Article  CAS  PubMed  Google Scholar 

  • Paul KN, Dugovic C et al (2006) Diurnal sex differences in the sleep–wake cycle of mice are dependent on gonadal function. Sleep 29(9):1211–1223

    PubMed  Google Scholar 

  • Refinetti R (2003) Metabolic heat production, heat loss and the circadian rhythm of body temperature in the rat. Exp Physiol 88(3):423–429

    Article  PubMed  Google Scholar 

  • Reynolds MA, Ingram DK et al (1985) Relationship of body temperature stability to mortality in aging mice. Mech Ageing Dev 30(2):143–152

    Article  CAS  PubMed  Google Scholar 

  • Rikke BA, Johnson TE (2004) Lower body temperature as a potential mechanism of life extension in homeotherms. Exp Gerontol 39(6):927–930

    Article  PubMed  Google Scholar 

  • Rikke BA, Johnson TE (2007) Physiological genetics of dietary restriction: uncoupling the body temperature and body weight responses. Am J Physiol Regul Integr Comp Physiol 293(4):R1522–R1527

    CAS  PubMed  Google Scholar 

  • Schriner SE, Linford NJ et al (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308(5730):1909–1911

    Article  CAS  PubMed  Google Scholar 

  • Selman C, Lingard S et al (2008) Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J 22(3):807–818

    Article  CAS  PubMed  Google Scholar 

  • Silberberg SD, Magleby KL (1999) Beating the odds with Big K. Science 285(5435):1859–1860

    Article  CAS  PubMed  Google Scholar 

  • Silva NL, Boulant JA (1986) Effects of testosterone, estradiol, and temperature on neurons in preoptic tissue slices. Am J Physiol 250(4 Pt 2):R625–R632

    CAS  PubMed  Google Scholar 

  • Sokolove PG, Bushell WN (1978) The chi square periodogram: its utility for analysis of circadian rhythms. J Theor Biol 72(1):131–160

    Article  CAS  PubMed  Google Scholar 

  • Sugama S, Kim Y et al (2000) Tissue-specific expression of rat IL-18 gene and response to adrenocorticotropic hormone treatment. J Immunol 165(11):6287–6292

    CAS  PubMed  Google Scholar 

  • Tabarean IV, Conti B et al (2005) Electrophysiological properties and thermosensitivity of mouse preoptic and anterior hypothalamic neurons in culture. Neuroscience 135(2):433–449

    Article  CAS  PubMed  Google Scholar 

  • Talan MI, Engel BT (1986) Temporal decrease of body temperature in middle-aged C57BL/6J mice. J Gerontol 41(1):8–12

    CAS  PubMed  Google Scholar 

  • Tower J, Arbeitman M (2009) The genetics of gender and life span. J Biol 8(4):38

    PubMed  Google Scholar 

  • Tsai CL, Matsumura K et al (1988) Effects of progesterone on thermosensitive neurons in preoptic slice preparations. Neurosci Lett 86(1):56–60

    Article  CAS  PubMed  Google Scholar 

  • Tsai CL, Kanosue K et al (1992) Effects of estradiol treatment on responses of rat preoptic warm sensitive neurons to progesterone in vitro. Neurosci Lett 136(1):23–26

    Article  CAS  PubMed  Google Scholar 

  • Turturro A, Witt WW et al (1999) Growth curves and survival characteristics of the animals used in the biomarkers of aging program. J Gerontol A Biol Sci Med Sci 54(11):B492–B501

    CAS  PubMed  Google Scholar 

  • van Baak MA (2008) Meal-induced activation of the sympathetic nervous system and its cardiovascular and thermogenic effects in man. Physiol Behav 94(2):178–186

    Article  PubMed  Google Scholar 

  • Vina J, Borras C et al (2005a) Why females live longer than males: control of longevity by sex hormones. Sci Aging Knowledge Environ 23:pe17

    Article  Google Scholar 

  • Vina J, Borras C et al (2005b) Why females live longer than males? Importance of the upregulation of longevity-associated genes by oestrogenic compounds. FEBS Lett 579(12):2541–2545

    Article  CAS  PubMed  Google Scholar 

  • Weinert D (1994) Lower variability in female as compared to male laboratory mice: investigations on circadian rhythms. J Exp Anim Sci 37:121–137

    Google Scholar 

  • Weinert D (2010) Circadian temperature variation and ageing. Ageing Res Rev 9(1):51–60

    Article  PubMed  Google Scholar 

  • Weinert D, Waterhouse J et al (2004) Changes of body temperature and thermoregulation in the course of the ovarian cycle in laboratory mice. Biol Rhythm Res 35(3):171–185

    Article  Google Scholar 

  • Yang JN, Tiselius C et al (2007) Sex differences in mouse heart rate and body temperature and in their regulation by adenosine A1 receptors. Acta Physiol Oxf 190(1):63–75

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by The Ellison Medical Foundation and NIH AG028040.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bruno Conti.

Electronic supplementary material

Below is the link to the electronic supplementary material.

11357_2010_9164_MOESM1_ESM.pdf

Supplemental Table 1 Cosinor analysis of circadian Tc and LMA profile female and male mice during hormone replacement. DHT, 5α-dihydrotestosterone; 17beta E, 17β-estradiol; TX, treated. (PDF 49 kb)

Fig4

Supplemental Figure 1 Profile of Tc and LMA of 3-month-old female mice indicating (arrows) the time of vaginal swabs collected for histological analysis for determination of estrous phases. A profile comprising 1 h before and 1 h after sample collection is shown in the lower panel. (GIF 171 kb)

High resolution image (EPS 1666 kb)

Fig5

Supplemental Figure 2 Tc and LMA profiles of castrated male and ovariectomized female treated with placebo or 5α-dihydrotestosterone (5αHDT) testosterone, progesterone, or 17β-estradiol (17βE) recorded over 24 h. (n = 6, 6; *p < 0.05). (GIF 311 kb)

High resolution image (EPS 6688 kb)

Fig6

Supplemental Figure 3 Survival curves of C57Bl/6 mice maintained in the same dietary and environmental conditions used for the mice used in the present study, showing that males outlived females. Vertical lines correspond to the age investigated in this study: 3 and 24 months. The curves were extrapolated from the study previously published by us (Conti et al. 2006). (EPS 781 kb) (GIF 37 kb)

High resolution image (EPS 781 kb)

About this article

Cite this article

Sanchez-Alavez, M., Alboni, S. & Conti, B. Sex- and age-specific differences in core body temperature of C57Bl/6 mice. AGE 33, 89–99 (2011). https://doi.org/10.1007/s11357-010-9164-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-010-9164-6

Keywords

Navigation