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.
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Supported by The Ellison Medical Foundation and NIH AG028040.
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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)
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)
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)
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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
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DOI: https://doi.org/10.1007/s11357-010-9164-6