, Volume 33, Issue 1, pp 89–99 | Cite as

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

  • Manuel Sanchez-Alavez
  • Silvia Alboni
  • Bruno Conti


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.


Temperature Gender Mouse Gonadectomy Locomotor activity 

Supplementary material

11357_2010_9164_MOESM1_ESM.pdf (50 kb)
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)
11357_2010_9164_Fig4_ESM.gif (172 kb)

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)

11357_2010_9164_MOESM2_ESM.eps (1.6 mb)
High resolution image (EPS 1666 kb)
11357_2010_9164_Fig5_ESM.gif (311 kb)

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)

11357_2010_9164_MOESM3_ESM.eps (6.5 mb)
High resolution image (EPS 6688 kb)
11357_2010_9164_Fig6_ESM.gif (38 kb)

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)

11357_2010_9164_MOESM4_ESM.eps (781 kb)
High resolution image (EPS 781 kb)


  1. Abe J, Okazawa M et al (2003) Primary cold-sensitive neurons in acutely dissociated cells of rat hypothalamus. Neurosci Lett 342(1–2):29–32CrossRefPubMedGoogle Scholar
  2. 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):565–574CrossRefPubMedGoogle Scholar
  3. Boulant JA (2006) Neuronal basis of Hammel's model for set-point thermoregulation. J Appl Physiol 100(4):1347–1354CrossRefPubMedGoogle Scholar
  4. Brown RE, Gander GW et al (1970) Estrogen and cortisone: effects on thermoregulation in the female rabbit. Proc Soc Exp Biol Med 134(1):83–86PubMedGoogle Scholar
  5. Brown-Borg HM, Borg KE et al (1996) Dwarf mice and the ageing process. Nature 384(6604):33CrossRefPubMedGoogle Scholar
  6. Carandente F, De Matteis MA et al (1982) Circadian temperature rhythm in intact, sham operated, gonadectomized rats. Chronobiologia 9(2):211–221PubMedGoogle Scholar
  7. Cargill SL, Carey JR et al (2003) Age of ovary determines remaining life expectancy in old ovariectomized mice. Aging Cell 2(3):185–190CrossRefPubMedGoogle Scholar
  8. 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):1–7CrossRefPubMedGoogle Scholar
  9. Conti B, Sanchez-Alavez M et al (2006) Transgenic mice with a reduced core body temperature have an increased life span. Science 314(5800):825–828CrossRefPubMedGoogle Scholar
  10. 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):409–421CrossRefPubMedGoogle Scholar
  11. Coschigano KT, Clemmons D et al (2000) Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 141(7):2608–2613CrossRefPubMedGoogle Scholar
  12. 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):3799–3810CrossRefPubMedGoogle Scholar
  13. 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):474–486CrossRefPubMedGoogle Scholar
  14. 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):13–17PubMedGoogle Scholar
  15. 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):59–64PubMedGoogle Scholar
  16. 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):6736–6741CrossRefPubMedGoogle Scholar
  17. 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):121–130CrossRefPubMedGoogle Scholar
  18. Fregly MJ, Kelleher DL et al (1979) Tolerance of estrogen-treated rats to acute cold exposure. J Appl Physiol 47(1):59–66PubMedGoogle Scholar
  19. 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):73–79CrossRefPubMedGoogle Scholar
  20. 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):84–97CrossRefPubMedGoogle Scholar
  21. Gordon CJ (1993) Temperature regulation in laboratory rodents. Cambridge University Press, New YorkCrossRefGoogle Scholar
  22. Gordon CJ (2008) Cardiac and thermal homeostasis in the aging Brown Norway rat. J Gerontol A Biol Sci Med Sci 63(12):1307–1313PubMedGoogle Scholar
  23. Griffin JD, Saper CB et al (2001) Synaptic and morphological characteristics of temperature-sensitive and -insensitive rat hypothalamic neurones. J Physiol 537(Pt 2):521–535CrossRefPubMedGoogle Scholar
  24. Hammel H (1965) Neurons and temperature regulation. In: Yamamoto WS, Brobeck JR (eds) Physiological controls and regulations. Saunders, Philadelphia, pp 71–97Google Scholar
  25. Holzenberger M, Dupont J et al (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421(6919):182–187CrossRefPubMedGoogle Scholar
  26. Hori A, Minato K et al (1999) Warming-activated channels of warm-sensitive neurons in rat hypothalamic slices. Neurosci Lett 275(2):93–96CrossRefPubMedGoogle Scholar
  27. Kruijver FP, Swaab DF (2002) Sex hormone receptors are present in the human suprachiasmatic nucleus. Neuroendocrinology 75(5):296–305CrossRefPubMedGoogle Scholar
  28. Kurosu H, Yamamoto M et al (2005) Suppression of aging in mice by the hormone Klotho. Science 309(5742):1829–1833CrossRefPubMedGoogle Scholar
  29. Ladiges W, Van Remmen H et al (2009) Lifespan extension in genetically modified mice. Aging Cell 8(4):346–352CrossRefPubMedGoogle Scholar
  30. Liu RK, Walford RL (1966) Increased growth and life-span with lowered ambient temperature in the annual fish, Cynolebias adloffi. Nature 212:1277–1278CrossRefGoogle Scholar
  31. 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):419–425CrossRefPubMedGoogle Scholar
  32. 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):1207–1211PubMedGoogle Scholar
  33. 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):1653–1662CrossRefPubMedGoogle Scholar
  34. Morrison SF, Nakamura K et al (2008) Central control of thermogenesis in mammals. Exp Physiol 93(7):773–797CrossRefPubMedGoogle Scholar
  35. Nakamura K, Morrison SF (2008) A thermosensory pathway that controls body temperature. Nat Neurosci 11(1):62–71CrossRefPubMedGoogle Scholar
  36. Nieschlag E, Nieschlag S et al (1993) Lifespan and testosterone. Nature 366(6452):215CrossRefPubMedGoogle Scholar
  37. 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):1211–1223PubMedGoogle Scholar
  38. Refinetti R (2003) Metabolic heat production, heat loss and the circadian rhythm of body temperature in the rat. Exp Physiol 88(3):423–429CrossRefPubMedGoogle Scholar
  39. Reynolds MA, Ingram DK et al (1985) Relationship of body temperature stability to mortality in aging mice. Mech Ageing Dev 30(2):143–152CrossRefPubMedGoogle Scholar
  40. Rikke BA, Johnson TE (2004) Lower body temperature as a potential mechanism of life extension in homeotherms. Exp Gerontol 39(6):927–930CrossRefPubMedGoogle Scholar
  41. 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–R1527PubMedGoogle Scholar
  42. Schriner SE, Linford NJ et al (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308(5730):1909–1911CrossRefPubMedGoogle Scholar
  43. 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):807–818CrossRefPubMedGoogle Scholar
  44. Silberberg SD, Magleby KL (1999) Beating the odds with Big K. Science 285(5435):1859–1860CrossRefPubMedGoogle Scholar
  45. 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–R632PubMedGoogle Scholar
  46. Sokolove PG, Bushell WN (1978) The chi square periodogram: its utility for analysis of circadian rhythms. J Theor Biol 72(1):131–160CrossRefPubMedGoogle Scholar
  47. 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):6287–6292PubMedGoogle Scholar
  48. Tabarean IV, Conti B et al (2005) Electrophysiological properties and thermosensitivity of mouse preoptic and anterior hypothalamic neurons in culture. Neuroscience 135(2):433–449CrossRefPubMedGoogle Scholar
  49. Talan MI, Engel BT (1986) Temporal decrease of body temperature in middle-aged C57BL/6J mice. J Gerontol 41(1):8–12PubMedGoogle Scholar
  50. Tower J, Arbeitman M (2009) The genetics of gender and life span. J Biol 8(4):38PubMedGoogle Scholar
  51. Tsai CL, Matsumura K et al (1988) Effects of progesterone on thermosensitive neurons in preoptic slice preparations. Neurosci Lett 86(1):56–60CrossRefPubMedGoogle Scholar
  52. 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):23–26CrossRefPubMedGoogle Scholar
  53. 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–B501PubMedGoogle Scholar
  54. van Baak MA (2008) Meal-induced activation of the sympathetic nervous system and its cardiovascular and thermogenic effects in man. Physiol Behav 94(2):178–186CrossRefPubMedGoogle Scholar
  55. Vina J, Borras C et al (2005a) Why females live longer than males: control of longevity by sex hormones. Sci Aging Knowledge Environ 23:pe17CrossRefGoogle Scholar
  56. 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):2541–2545CrossRefPubMedGoogle Scholar
  57. Weinert D (1994) Lower variability in female as compared to male laboratory mice: investigations on circadian rhythms. J Exp Anim Sci 37:121–137Google Scholar
  58. Weinert D (2010) Circadian temperature variation and ageing. Ageing Res Rev 9(1):51–60CrossRefPubMedGoogle Scholar
  59. 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):171–185CrossRefGoogle Scholar
  60. 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):63–75CrossRefPubMedGoogle Scholar

Copyright information

© American Aging Association, Media, PA, USA 2010

Authors and Affiliations

  • Manuel Sanchez-Alavez
    • 1
  • Silvia Alboni
    • 2
  • Bruno Conti
    • 1
  1. 1.Molecular and Integrative Neurosciences DepartmentThe Scripps Research InstituteLa JollaUSA
  2. 2.Biomedical Sciences DepartmentUniversity of Modena and Reggio EmiliaModenaItaly

Personalised recommendations