Greer Kimberly A, Hughes Larry M, Masternak Michal M
Indiana University East, 2325 Chester Blvd, Richmond, IN 47374, USA.
Age (Dordr). 2011 Sep;33(3):475-83. doi: 10.1007/s11357-010-9182-4. Epub 2010 Sep 24.
Many investigations in recent years have targeted understanding the genetic and biochemical basis of aging. Collectively, genetic factors and biological mechanisms appear to influence longevity in general and specifically; reduction of the insulin/IGF-1 signaling cascade has extended life span in diverse species. Genetic alteration of mammals for life extension indicates correlation to serum IGF-1 levels in mice, and IGF-1 levels have been demonstrated as a physiological predictor of frailty with aging in man. Longevity and aging data in the dog offer a close measure of the natural multifactorial longevity interactions of genetic influence, IGF-1 signaling, and environmental factors such as exposure, exercise, and lifestyle. The absence of genetic alteration more closely represents the human longevity status, and the unique species structure of the canine facilitates analyses not possible in other species. These investigations aimed to measure serum IGF-1 in numerous purebred and mixed-breed dogs of variable size and longevity in comparison to age, gender, and spay/neuter differences. The primary objective of this investigation was to determine plasma IGF-1 levels in the adult dog, including a wide range of breeds and adult body weight. The sample set includes animals ranging from just a few months of age through 204 months and ranging in size from 5 to 160 lb. Four groups were evaluated for serum IGF-1 levels, including intact and neutered males, and intact and spayed females. IGF-1 loss over time, as a function of age, decreases in all groups with significant differences between males and females. The relationship between IGF-1 and weight differs depending upon spay/neuter status, but there is an overall increase in IGF-1 levels with increasing weight. The data, currently being interrogated further for delineation of IGF-1 receptor variants and sex differences, are being collected longitudinally and explored for longevity associations previously unavailable in non-genetically modified mammals.
近年来,许多研究致力于了解衰老的遗传和生化基础。总体而言,遗传因素和生物学机制似乎对寿命有着普遍且特定的影响;胰岛素/IGF-1信号级联反应的减弱已在多种物种中延长了寿命。哺乳动物为延长寿命而进行的基因改造表明与小鼠血清IGF-1水平相关,并且IGF-1水平已被证明是人类衰老过程中身体虚弱的生理预测指标。狗的寿命和衰老数据为遗传影响、IGF-1信号传导以及暴露、运动和生活方式等环境因素之间自然的多因素寿命相互作用提供了一个相近的衡量标准。没有基因改造更接近人类的长寿状况,并且犬类独特的物种结构便于进行其他物种无法进行的分析。这些研究旨在测量众多不同体型和寿命的纯种和混种狗的血清IGF-1,并与年龄、性别以及绝育/去势差异进行比较。这项研究的主要目的是确定成年犬的血浆IGF-1水平,包括广泛的品种和成年体重范围。样本集包括年龄从几个月到204个月不等、体重从5磅到160磅不等的动物。对四组动物的血清IGF-1水平进行了评估,包括未绝育和绝育的雄性以及未绝育和绝育的雌性。随着时间推移,IGF-1随年龄下降,所有组均如此,且雄性和雌性之间存在显著差异。IGF-1与体重的关系因绝育/去势状态而异,但随着体重增加,IGF-1水平总体上会升高。目前正在进一步研究这些数据,以确定IGF-1受体变体和性别差异,这些数据是纵向收集的,并探索非基因改造哺乳动物中以前无法获得的与长寿的关联。