热量限制延缓衰老的机制研究进展

热量限制（Caloric restriction,CR）指在提供生物体充足的营养成分如必需氨基酸、维生素等,保证生物体不发生营养不良的情况下,限制每日摄取的总热量,又称为饮食限制（Dietary restriction,DR）。     

饮食限制延缓衰老的研究进展

目前随着经济发展及生活水平的不断提高,中国老龄化情况日益严重,各种衰老相关疾病的发病率也呈直线上升。因此,寻找有效的延缓衰老方法、预防老年病的发生越来越受到人们的关注。近几年研究表明,饮食限制(DR)可以有效地延长哺乳动物的寿命,同时延缓老年病的发生。在避免营养不良的前提下对饮食摄入进行限制,现今已成为抗衰老领域的一大热门方向。本文就DR在延缓衰老中的作用及其可能机制的研究进展作一综述。     

热量限制延缓衰老作用机制的研究进展

自1935年Mccay等发现适度限食可以延长大鼠寿限(1ife span)以来，许多实验不断证实，啮齿类动物从幼年开始，每天限制正常摄食量的30％～50％，不但不引起营养不良，还可以比正常摄食组延长30％～50％的平均和最高寿命；从成年或成年以上开始同样的限食，可以延长小鼠的最高寿限10％～20％。同时发现热量限制(caloric     

热量限制延缓衰老及其在人类中的实践

热量限制(Caloric restriction,CR)指在提供生物体充分的营养成分如必需氨基酸、维生素等,保证生物体不发生营养不良的情况下,限制每日摄取的总热量,又称为饮食限制(Dietaryrestriction,DR)〔1〕。McCay等〔2〕于1935年首次报道CR延长大鼠寿限,迄今70余年来,大量实验已表明CR是除遗传操作以外最强有力的延缓衰老方法,被称为衰老研究领域最重大的发现〔3〕。同时CR还推迟和降低多种老龄相关疾病如肿瘤、心血管疾病、2型糖尿病等发病〔4〕。CR已经成为衰老机制及干预措施研究的一个重要模型,并且已有不少研究探索如何在人类实行CR。为…     

阿卡波糖通过模拟热量限制延缓衰老：降糖之外的惊喜

热量限制(CR)在延缓衰老、防治2型糖尿病、肥胖等代谢性疾病中的意义和优势不言而喻,然而,长期实施CR依然面临很大挑战。热量限制模拟剂(CRMs)旨在不限制饮食的基础上模拟CR的效果,通过调节能量代谢、激活自噬、调控长寿基因表达等途径达到抗衰老的作用。阿卡波糖作为一种广泛使用的降糖药物,在临床和基础研究中被初步证实可以延长寿命、延缓肿瘤生长、减少衰老相关疾病的发生,故有望成为CRMs候选药物之一。本文主要从CR模拟角度探讨阿卡波糖延缓衰老的可能机制,为其助力人类健康提供初步理论依据。     

延缓衰老汤对衰老模型大鼠的保护作用

目的探讨延缓衰老汤(YT)对D-半乳糖所致衰老大鼠的保护作用。方法选择健康SD大鼠40只,平均分成正常对照组、模型组、阳性对照组和给药组。其中正常对照组不做任何处理,其余三组大鼠腹腔注射D-半乳糖和生理盐水建立亚急性衰老模型,同时,阳性对照组灌胃维生素E,给药组大鼠灌胃YT混悬液,正常对照组和模型组给予等量生理盐水,连续培养2个月后,测定所有大鼠肝、脑组织中丙二醇(MDA)和超氧化物歧化酶(SOD)含量、外周血清白细胞介素(IL)-2含量及腹腔巨噬细胞吞噬中性红能力指标。结果与正常对照组大鼠相比,模型组大鼠肝、脑组织中MDA含量明显升高,SOD含量均显著下降(P0.01);与模型组相比,阳性对照组和给药组肝、脑组织中MDA的含量明显降低,SOD的含量明显提高(P0.01)。模型组大鼠血清IL-2的含量明显低于正常对照组(P0.01);而阳性对照组和给药组大鼠血清IL-2含量均显著高于模型组(P0.01)。模型组吸光度A值明显低于正常对照组(P0.01);而阳性对照组和给药组吸光度A值均显著高于模型组(P0.01)。结论 YT通过降低肝、脑组织中MDA含量,提高SOD含量,提高血清中IL-2含量和腹腔巨噬细胞的吞噬能力来延缓D-半乳糖所致的大鼠衰老。     

胸腺素在延缓衰老中的免疫调节作用

胸腺素是在由胸腺上皮细胞合成和分泌的多种生化性质不同的具体激素样活性的多肽类物质的总称。胸腺是衰老中心,胸腺素具有延缓衰老的作用。本文从延缓机体免疫衰老的角度阐述了胸腺素对胸腺、T淋巴细胞、B淋巴细胞、红细胞、LAK细胞、NK细胞的免疫调节作用。     

延缓衰老的综合对策

衰老是人类生命过程的必然规律 ,是不可抗拒的 ,但推迟衰老的发生、发展是十分必要 ,也是完全可能的。欲想延缓衰老 ,必须掌握衰老的规律。衰老的基本原因是遗传 ,而衰老机理则是代谢失调[1,2 ] 。衰老是机体内外环境诸多因素相互作用的结果。因此 ,欲求推迟衰老就必须了解妨碍细胞代谢的种种因素 ,并设法把这些因素减少或去除。2 0 0 1年美国国立科学院院报报道[3 ] ,经过 137个长寿家庭中 30 8名年龄在 90～ 10 9岁长寿老人血样品研究发现 ,他们的第 4号染色体都有一段与普通人不同的区域 ,该区域包括一些基因 ,对这些基因结构进行分析 ,…     

常吃低热量食物能延缓衰老

长期摄取低热量食物并注意营养均衡是延缓身体衰老尤其是延缓心脏衰老的新方法。据报道，对25位年龄在41岁至65岁之间的志愿者进行了跟踪调查。这些人在最近6年中一直注重营养平衡，并且吃低热量的食物，他们每天摄取的食物热量为1400至1950卡路里。同时，研究人员还对另外一组同龄的25位志愿者进行了观察，他们每天摄取的食物热量为2000至3500卡路里。调查显示，摄取较少热量的那组人的心脏更富有弹性，心脏跳动情况接近于比他们年轻的人的心脏状况。     

胸腺因子D延缓衰老的作用和机理

胸腺因子Ｄ延缓衰老的作用和机理陈紫榕刘小朋陈少华李林１张国安温云海杨才生施水兰傅文庆２（解放军第４７６医院，福州３５０００２）１北京市老年医学研究所２福建师范大学生物工程学院作者简介：陈紫榕，男，５９岁，主任医师、教授，从事传染病、免疫和胸腺激素基础...     

Effect of a caloric restriction regimen on the angiogenic capacity of aorta and on the expression of endothelin-1 during ageing

Ageing is accompanied by impaired angiogenesis, as well as by a deficient expression of several angiogenic growth factors and the alteration of endothelial functions. Caloric restriction (CR) is the only intervention that can extend lifespan and retard age-related-decline functions in mammals by reducing the rate of ageing and the progression of the associated diseases. Herein, we have investigated the effects of ageing and of a caloric restriction regimen (mild or severe) on the angiogenic response and on the expression of endothelin-1 (ET-1) in the aorta of male 3-, 12- or 24-month-old Sprague-Dawley rats fed ad libitum (AL), fed ad libitum and fasted 1 day a week (mild CR) or fasted every other in alternate days (severe CR). Our findings, using the rat aorta ring assay, show that the angiogenic capacity of aorta decreases with ageing in the oldest rats only. Furthermore, caloric restriction counteracts the age-related changes caloric restrictions actually give raise to a similar recovery. Interestingly, the mRNA ET-1 levels as well as ET-1 expression in aorta sprouting decreases both in middle and in aged animals. Mild and severe caloric restriction regimens prevents ET-1 changes.     

Recent advances in calorie restriction research on aging

The extension of both median and maximum lifespan and the suppression of age-related diseases in laboratory animals by reduced food intake, i.e., calorie restriction (CR) are regarded as hallmarks of CR's anti-aging action. The diverse efficacy of CR to counteract aging effects and its experimental reproducibility has made it the gold standard of many aging intervention studies of recent years. Although CR originally was used as a tool to perturb the aging process of laboratory animals as to uncover clues of underlying mechanisms of aging processes, current CR research interests have shifted to the retardation of aging-related functional decline and the prevention of age-related diseases. Advances in CR research on non-human primates and recent endeavors using human subjects offer a promising outlook for CR's beneficial effects in healthy human aging.     

Skeletal effects of long-term caloric restriction in rhesus monkeys

Age-related bone loss is well established in humans and is known to occur in nonhuman primates. There is little information, however, on the effect of dietary interventions, such as caloric restriction (CR), on age-related bone loss. This study examined the effects of long-term, moderate CR on skeletal parameters in rhesus monkeys. Thirty adult male rhesus monkeys were subjected to either a restricted (R, n = 15) or control (C, n = 15) diet for 20 years and examined throughout for body composition and biochemical markers of bone turnover. Total body, spine, and radius bone mass and density were assessed by dual-energy X-ray absorptiometry. Assessment of biochemical markers of bone turnover included circulating serum levels of osteocalcin, carboxyterminal telopeptide of type I collagen, cross-linked aminoterminal telopeptide of type I collagen, parathyroid hormone, and 25(OH)vitamin D. Overall, we found that bone mass and density declined over time with generally higher levels in C compared to R animals. Circulating serum markers of bone turnover were not different between C and R with nonsignficant diet-by-time interactions. We believe the lower bone mass in R animals reflects the smaller body size and not pathological osteopenia.     

The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction

Hydrogen sulfide gas (H₂S) is a putative signaling molecule that causes diverse effects in mammalian tissues including relaxation of blood vessels and regulation of perfusion in the liver, but the effects of aging on H₂S signaling are unknown. Aging has negative impacts on the cardiovascular system. However, the liver is more resilient with age. Caloric restriction (CR) attenuates affects of age in many tissues. We hypothesized that the H₂S signaling system is negatively affected by age in the vasculature but not in the liver, which is typically more resilient to age, and that a CR diet minimizes the age affect in the vasculature. To investigate this, we determined protein and mRNA expression of the H₂S-producing enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), H₂S production rates in the aorta and liver, and the contractile response of aortic rings to exogenous H₂S. Tissue was collected from Fisher 344 × Brown Norway rats from 8–38 months of age, which had been maintained on an ad libitum (AL) or CR diet. The results demonstrate that age and diet have differential effects on the H₂S signaling system in aorta and liver. The aorta showed a sizeable effect of both age and diet, whereas the liver only showed a sizeable effect of diet. Aortic rings showed increased contractile sensitivity to H₂S and increased protein expression of CSE and CBS with age, consistent with a decrease in H₂S concentration with age. CR appears to benefit CSE and CBS protein in both aorta and liver, potentially by reducing oxidative stress and ameliorating the negative effect of age on H₂S concentration. Therefore, CR may help maintain the H₂S signaling system during aging.     

Effects of caloric restriction are species-specific

This article addresses two questions: (1) ‘can caloric restriction (CR) extend the life spans of all species of experimental animals’, and (2) ‘is CR likely to slow the human aging process and/or extend the human life span?’ The answer to the first question is clearly ‘no’, because CR decreases the life span of the housefly, Musca domestica, and fails to extend the life span of at least one mouse strain. The answer to the second question is unknown, because human CR has not yet been shown either to increase or curtail the human life span. However, recent efforts to develop insect models of CR have been unsuccessful and/or relatively uninformative, so any insights regarding the relationship between CR and human aging are more likely to arise from studies of established, mammalian models of CR.     

限制能量摄入对大鼠胰岛细胞衰老及胰岛素表达的影响

目的 探讨限制能量摄人对大鼠胰岛细胞衰老及胰岛素表达的影响.方法 18月龄SD大鼠经过限制能量摄入(给予正常饮食量的60%)6个月,建立限制能量摄入动物模型.取限制能量摄人组(实验组)及对照组胰腺,行β-半乳糖苷酶(SA-β-Gal)染色并检测胰岛内p16的表达,以了解胰岛细胞衰老状态;同时检测胰岛B细胞胰岛素的表达.结果 实验组与对照组比较,胰岛内p16表达减少,分别为(0.19130±0.02852)个和(0.24526±0.03191)/p,差异有统计学意义(P＜0.01);胰岛内β-Gal染色阳性率分别为84%和100%(P＜0.01)、着色面积1.672和2.118(P＜0.05)、着色程度1.725和2.412(P＜0.05);胰岛素表达增加(201.7±35.3和187.8±26.0),差异有统计学意义(P＜0.05)结论限制能量摄入可延缓胰岛B细胞衰老,改善胰岛的分泌功能.     

Facts and controversies in our understanding of how caloric restriction impacts the mitochondrion

Caloric restriction (CR) has pronounced benefits in promoting healthy aging. Amongst the most frequently implicated physiological mechanisms implicated in this benefit is altered mitochondrial function. Whereas a reduction in mitochondrial reactive oxygen species (ROS) production is a widely consistent effect of CR, an increase in mitochondrial biogenesis, which is accepted by many as fact, is contradicted on several levels, most critically by a lack of increase in mitochondrial protein synthesis rate in vivo. Furthermore, an increase in PGC-1α protein and markers of mitochondrial content with CR is a highly variable observation between studies. On the other hand, deacetylation of several mitochondrial proteins by the sirtuin, Sirt3, is an increasingly reported observation and at least so far, this observation is consistent between studies. Notwithstanding this point, the controversies evident in the published literature underscore the significant questions that remain in our understanding of how CR impacts the mitochondrion and suggest we have yet to fully understand the complexities herein.     

Health span extension by later-life caloric or dietary restriction: a view based on rodent studies

In spite of the potential benefit of lifelong food restriction to retard aging and extend life span, it is unrealistic in human. The restriction late in life may be more practical. There are, however, only limited studies on the effect of late onset caloric or dietary restriction. We and other investigators have shown that the late life restriction rejuvenates some parameters that decline with age in rats and mice. Although such studies may provide a basis for human application of late-life caloric or dietary restriction, the prolongation of maximum life span would not be expected in view of the current status of the long-lived population in which maximum life span potential appears to have already been achieved. The late life caloric restriction, however, could extend the health span if the extent were appropriate.     

限食疗法对非酒精性脂肪性肝病的治疗作用

作为一种代谢性疾病,非酒精性脂肪性肝病的治疗主要是生活方式干预.限食疗法作为生活方式干预的一种,已被证实可减轻患者的体重、减少肝脏内脂肪含量、减轻胰岛素抵抗,改善其他代谢异常.而且,有研究认为,不同方式的限食对该病的治疗效果存在差异,低脂及低碳水化合物限食对其治疗效果优于低热量限食,这值得进一步研究探索.