Sanchez-Alavez Manuel, Alboni Silvia, Conti Bruno
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Age (Dordr). 2011 Mar;33(1):89-99. doi: 10.1007/s11357-010-9164-6. Epub 2010 Jul 16.
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.
跨物种均有报道寿命存在性别差异,其由尚未完全明确的机制介导。在衰老研究中常用的C57Bl/6小鼠中,雄性通常比雌性寿命长。由于在这些动物中适度但长期降低核心体温(Tc)可延长寿命,我们推测Tc的差异可能导致性别特异性的寿命差异。在此,我们比较了雄性和雌性C57Bl/6小鼠的Tc昼夜节律和运动活动(LMA)。由于Tc和LMA通常会随年龄变化,因此在年轻(3个月)和年老(24个月)小鼠中均进行了测量。在年轻雌性小鼠中,Tc受发情期影响,但总体上高于雄性。在消除了与发情期相关的变化的老年动物中,这种差异更大。尽管体温稳态由具有性别差异的下丘脑视前区进行中枢调节,但这些差异独特地依赖于性腺。事实上,双侧性腺切除术消除了发情期的影响,并提高了雄性的静息Tc,消除了Tc和LMA中所有的性别特异性差异。激素替代仅部分模拟了这些效应,因为Tc受孕酮影响,受雌激素影响较小,但不受睾酮影响。因此,性腺依赖性的Tc调节可能是导致寿命性别特异性差异的生理参数之一。