D-半乳糖致衰老动物模型的建立及评价

建立衰老动物模型是研究人类衰老过程的有效方法.结合动物的生理特性及自然属性,建立不同的动物模型,已成为衰老及抗衰老研究的焦点.D-半乳糖衰老动物模型与其他几种衰老动物模型（如自然衰老模型、臭氧损伤衰老模型、去胸腺衰老模型、SAMP系小鼠衰老模型等）相比,简便易行,价格低廉,结果稳定,因而得到广泛应用.结合该模型近年来的运用和发展,本文对该模型构建原理、剂量、具体方法和评估手段作一综述,并对行为学水平、生化水平、形态学水平、分子生物水平检测指标进行总结.总之,采用D-半乳糖120～125mg/（ kg·d）连续皮下注射6～8周是较为可靠、稳定的建立衰老动物模型的方法.     

卷丹水提物对D-半乳糖衰老模型小鼠的影响

目的观察卷丹水提物对D-半乳糖衰老模型小鼠的影响。方法建立D-半乳糖致小鼠衰老模型，以Y型电迷宫检测其学习记忆能力，分别采用黄嘌呤氧化酶法、TBA比色法测定大脑SOD活性和MDA含量，观察小鼠服用卷丹水提物后上述指标的变化。结果与D-半乳糖模型组相比，卷丹水提物低、中、高剂量均可显著提高衰老模型小鼠的学习记忆能力（P〈0．05或P〈0．01），显著增加D-半乳糖所致衰老模型小鼠大脑SOD活性、降低MDA含量（P〈0．05）。结论卷丹水提物能改善D-半乳糖所致衰老小鼠的多项体征。     

D-半乳糖引起人正常二倍体细胞衰老的机制

目的 研究D-半乳糖处理后引起人正常二倍体细胞衰老的机制.方法 MTT法检测细胞存活率,衰老相关的β-半乳糖苷酶染色鉴定衰老细胞,流式细胞术检测细胞内活性氧自由基水平,免疫印迹法检测衰老相关蛋白的表达.结果 D-半乳糖处理人胚胎肺细胞和肝细胞,均能抑制细胞的增殖.被处理的细胞衰老相关的β-半乳糖苷酶染为蓝色,细胞内活性氧自由基水平明显升高,衰老信号通路相关蛋白p53、p21、caviolin-1的表达均升高.结论 D-半乳糖引起人正常二倍体细胞出现典型的细胞衰老表型,可以作为衰老的可靠模型.     

神经生长液对D-半乳糖衰老模型小鼠的影响

目的　观察中药合剂神经生长液对 D-半乳糖衰老模型小鼠的影响。方法　建立 D-半乳糖致小鼠衰老模型 ,以 Y型电迷宫检测其学习记忆能力 ,分别采用黄嘌呤氧化酶法、TBA比色法测定大脑 SOD活性和 MDA含量 ,观察小鼠服用神经生长液后上述指标的变化。结果　与 D-半乳糖模型组相比 ,神经生长液低、中、高剂量均可显著提高衰老模型小鼠的学习记忆能力 (P<0 .0 5或 P<0 .0 1 ) ,显著增加 D-半乳糖所致衰老模型小鼠大脑 SOD活性、降低 MDA含量 (P<0 .0 5或 P<0 .0 1 )。结论　神经生长液能改善 D-半乳糖所致衰老小鼠的多项体征。     

通补1号对D-半乳糖衰老模型大肠菌群的影响

目的研究通补Ⅰ号对D-半乳糖衰老小鼠模型的大肠杆菌群的影响。方法采用20±28ICR品系小鼠用D-半乳糖造模,同时用通补Ⅰ号治疗,采用滴注法检测衰老模型小鼠大肠杆菌、双歧杆菌及拟杆菌数量。结果D-半乳糖衰老模型大肠杆菌群中大肠杆菌增多,拟杆菌、双歧杆菌变化不大,通补Ⅰ号具有防治此模型肠杆菌增多的作用。结论通补Ⅰ号可通过抑制肠杆菌的产生,达到延缓衰老之功效。     

蜂胶总黄酮对衰老小鼠学习记忆的影响

目的 观察蜂胶总黄酮对D-半乳糖诱导衰老模型小鼠学习记忆的影响,并对其作用机制进行了探讨.方法 小鼠颈背部皮下注射D-半乳糖42 d,制备衰老模型.通过小鼠学习记忆能力、脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、脂褐素(LF)水平的测定,评价蜂胶总黄酮的抗衰老作用.结果 与空白对照组相比,D-半乳糖(150 g/kg,sc,42 d)使小鼠学习记忆能力降低,脑组织中SOD、GSH-Px活性下降,MDA、LF含量增加,而蜂胶总黄酮30 mg/kg、60 mg/kg和90 mg/kg三个剂量组对上述病理变化具有不同程度改善作用.结论 蜂胶总黄酮能改善D-半乳糖诱导衰老小鼠学习记忆功能障碍,其机制可能是抗氧化调节自由基代谢.     

双歧杆菌上清液对D-半乳糖的抗衰老作用

目的 通过观察双歧杆菌上清液(SCS)对D-半乳糖所致亚急性衰老小鼠血脂和学习记忆行为的影响,探讨SCS降低血脂的机制,为进一步研究SCS中有效延缓衰老的成分提供理论依据.方法 小鼠颈背部皮下注射D-半乳糖和生理盐水建立亚急性衰老模型和正常对照.同时,对实验组小鼠腹腔注射SCS,连续培养42 d后称重,检测血清中总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白(HDL-C) 含量.结果 与模型组相比,实验组小鼠血清TG、TC水平显著降低(P<0.05),血清HDL-C水平明显提高,学习记忆能力较模型组明显提高.结论 SCS能降低血清TG、TC含量,延缓D-半乳糖小鼠的衰老进程.     

补充维生素D对D-半乳糖诱导的衰老大鼠睾丸功能的改善作用及机制

目的:探讨补充维生素D对D-半乳糖诱导的衰老大鼠睾丸功能的作用及可能机制。方法:利用皮下注射D-半乳糖诱导衰老大鼠模型,将实验动物随机分为6组：衰老(DG)组、衰老+低剂量维生素D补充(LD)组、衰老+高剂量维生素D补充(HD)组、正常对照组(NC)、正常+低剂量维生素D补充(LN)组、正常+高剂量维生素D补充(HN)...     

地锦草总黄酮对老化模型小鼠血清衰老指标的影响

目的探讨地锦草总黄酮（TFEH）对老化模型小鼠的抗衰老作用机制。方法D-半乳糖致亚急性衰老模型小鼠共40d,分为正常对照组、模型组、TFEH大、小剂量组,检测各组小鼠血清丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）水平变化。结果TFEH能显著降低D-半乳糖致亚急性衰老模型小鼠血清MDA水平（P〈0.01）,能明显升高血清SOD、GSH-Px活性（P〈0.01）。结论TFEH可通过抗氧化作用而延缓衰老。     

中药PT液对衰老小鼠脑组织Ca2+含量的影响及机制探讨

目的　观察中药 PT液对衰老小鼠脑组织 Ca2 含量的影响 ,并探讨其可能机制。方法　 D-半乳糖衰老模型小鼠灌胃给予中药 PT液 ,测定脑组织 Ca2 含量、血清胰岛素水平、Na - ATP酶、Ca2 - ATP酶活性。结果　小鼠脑组织 Ca2 含量降至正常 ,血清胰岛素水平、Ca2 - ATP酶、Na - ATP酶活性均明显升高 ,与 D-半乳糖衰老模型组有显著性差异。结论　提高血清胰岛素水平 ,增强 Na - ATP酶、Ca2 - ATP酶活性 ,降低衰老小鼠脑组织内 Ca2 是 PT液抗衰老的重要机制。     

Oxidative stress: Its potential relevance to human disease and longevity determinants

Most evidence indicates that aging is a result of normal metabolic processes that are essential for life. Thus an important approach in biogerontology is to identify specific metabolic reactions necessary for life but which could also lead to aging. A unique characteristic of this approach is an explanation of what governs aging rate or longevity of a species or even individuals within a species. These would be mechanisms that would act to reduce the long-term toxic or aging effects of the normal metabolic and developmental reactions. The reactions involving oxygen metabolism clearly fit into this model for they are essential for life yet can potentially cause many of the dysfunctions associated with aging. Such a model can also account for differences in aging rate or longevity of different animal species by differences that may exist in their innate ability to reduce oxidative stress state. Our laboratory has been testing this oxidative stress state (OSS) hypothesis of aging and longevity by determining if a positive correlation exists between OSS of an animal and its aging rate. Much of our data has found such a positive correlation, yet there is some indication that separate causative mechanisms may exist in determining aging rate as opposed to those related to age-dependent specific diseases such as cancer or cardiovascular disease.     

Melatonin reduces memory changes and neural oxidative damage in mice treated with D-galactose

To investigate the role of melatonin in D-galactose-induced amnesic mice, the avoidance/escape and water maze tests were performed to evaluate their learning and memory function. Spectrophotometry was employed to determine the content of thiobarbituric acid-reactive substances (TBARS) and the activities of antioxidative enzymes in the brain. The present results demonstrate that D-galactose-induced amnesic mice had significantly decreased learning and memory function. The reduced activities of superoxide dismutase and glutathione peroxidase and increased levels of TBARS were found in brain tissue of the amnesic mice. Melatonin, administered (ig) at doses of 0.1, 1, or 10 mg/kg to the D-galactose-treated mice for 3 months, was sufficient to block these changes. These data suggest that D-galactose is involved in accelerating the brain aging process by elevating free radical generation and reducing antioxidative enzyme activities in vivo. Furthermore, the antioxidative activity of melatonin on the D-galactose-treated mice may account for, at least partially, the improvement of learning and memory function in the aging and amnesic model.     

Comparative and alternative approaches and novel animal models for aging research

This special issue of AGE showcases powerful alternative or unconventional approaches to basic aging research, including the use of exceptionally long-lived animal model species and comparative methods from evolutionary biology. In this opening paper, we introduce several of these alternative aging research themes, including the comparative phylogenetic approach. This approach applies modern inferential methods for dissecting basic physiological and biochemical mechanisms correlated with phenotypic traits including longevity, slow aging, sustained somatic maintenance, and repair of molecular damage. Comparative methods can be used to assess the general relevance of specific aging mechanisms—including oxidative processes—to diverse animal species, as well as to assess their potential clinical relevance to humans and other mammals. We also introduce several other novel, underexploited approaches with particular relevance to biogerontology, including the use of model animal species or strains that retain natural genetic heterogeneity, studies of effects of infectious disease and parasites on aging and responses to caloric restriction, studies of reproductive aging, and naturally occurring sex differences in aging. We emphasize the importance of drawing inferences from aging phenomena in laboratory studies that can be applied to clinically relevant aging syndromes in long-lived, outbred animals, including humans.     

Novel mechanisms responsible for postmenopausal hypertension

Blood pressure increases in many women after menopause. Hypertension is one of the major risk factors for cardiovascular disease. However, the mechanisms responsible for the postmenopausal increase in blood pressure are yet to be elucidated. Various humoral systems have been proposed to play a role in postmenopausal hypertension, such as changes in estrogen/androgen ratios, increases in endothelin and oxidative stress, and activation of the renin-angiotensin system (RAS). In addition, obesity, type II diabetes, and activation of the sympathetic nervous system are common in postmenopausal women and may also play important roles. However, progress in elucidating the mechanisms responsible for postmenopausal hypertension has been hampered by the lack of a suitable animal model. The aging female spontaneously hypertensive rat (SHR) exhibits many of the characteristics found in postmenopausal women. In this review, some of the possible mechanisms that could play a role in postmenopausal hypertension are discussed, as well as the characteristics of the aged female SHR as a model to study.     

Support for basic gerontological research in the USA

Support for research in basic gerontology in the United States of America is briefly described. The support mechanisms, how to apply for a grant, and priority areas of research are outlined, and recent progress in a few of these priority areas is discussed. In general, government support for biogerontology research has been generous, and as a result considerable progress has been made in understanding the molecular mechanisms of aging in animal model systems. Translation of these findings to humans, and development of interventions to promote healthy aging in humans remain an unfulfilled priority, but new knowledge and development of better technologies and model systems suggest an optimistic future.     

DNA损伤在衰老相关疾病中的研究进展

DNA损伤是衰老相关疾病领域的研究热点,可引起细胞周期停滞、凋亡,加快个体衰老速度、增加衰老相关疾病的患病风险。本文将从细胞衰老和个体衰老两个层面阐述其与衰老之间的研究进展,并综述其与衰老常见相关疾病(肿瘤、心血管疾病、阿尔茨海默病)及早衰综合征的关系,为抗衰老研究和临床干预衰老相关疾病提供理论依据。     

Birds as long-lived animal models for the study of aging

Despite their high lifetime energy expenditures, most birds can be characterized as long-lived homeotherms with moderately slow aging. A growing body of research confirms the prediction that birds have special adaptations for preventing aging-related oxidative and glycoxidative damage. Nonetheless, biogerontologists have been slow to develop avian laboratory models. A number of domestic poultry and cage bird species represent either established or very promising animal models for studies of basic aging processes and their prevention, including degenerative neurobiological, behavioral and reproductive processes. Several kinds of birds have also been used in studies of cellular resistance to oxidative stressors in vitro. Results of preliminary studies on chickens and quail suggest that caloric restriction may extend the reproductive life span of hens, but its long-term effects on life span remain unstudied. Birds' innate anti-aging mechanisms may actually make them more suitable in some respects as models of longevity than short-lived laboratory rodents, and bird studies may ultimately reveal routes for therapeutic intervention in diseases of human aging and infertility.     

Compensatory plasticity of aging at the neuromuscular junction.

Several age-related phenomena observed at the neuromuscular junction (NMJ) can be viewed as adaptations to cellular deficits. These compensatory mechanisms, which maintain functional and morphologic integrity, are those present in the adult animal. In the study of compensatory mechanisms with age, the choice of an appropriate animal model is important. Three adaptations are discussed: maintenance or increase of transmitter release despite reduced supply of synaptic vesicles; functional reactive sprouting after partial denervation despite reduced axonal transport; and maintenance of nerve terminal integrity in the face of increased outgrowth and retraction. In all cases, successful adaptation in old animals is obtained at the expense of a more fragile system. Either the compensations themselves or the resulting vulnerability may alter the reactions of the aging nervous system to changes in external and internal milieu.     

New findings in transgenic, gene knockout and mutant mice

Mice with experimentally induced or spontaneous genetic alterations continue to provide new and often unexpected information on the mechanisms of mammalian aging. Papers published during the last year (July 1, 2005 through June 30, 2006) contain many exciting findings, including development and characterization of a new animal model for the study of aging. Highlights of these recent developments will be briefly discussed in this Review.