饮食热量限制延缓衰老作用的研究进展

本文综述热量限制延缓衰老及其机制.无论是整体动物还是器官组织或细胞水平的研究均提示热量限制能延缓衰老,但其机制至今不明.目前有能量代谢理论、氧化应激理论、神经内分泌假说和细胞凋亡抑制等几种解释,并得到一定的实验研究支持,但没有一种理论能完全阐明热量限制延缓衰老的现象,在将实验研究结果推广于临床前仍有许多工作要做.     

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。     

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。     

SIRT1去乙酰化酶在热量限制法中的作用机制

在延缓衰老的研究中,热量限制是目前唯一经过科学实验证实有效的方法,研究显示长寿基因SIRT1去乙酰化酶在此过程中发挥了重要的作用.SIRT1通过将P53、FOXO3a和Ku70等蛋白去乙酰化而抑制细胞凋亡,通过作用于PGC-1α和PPAR-γ等蛋白来调节糖代谢和脂肪代谢.本文就热量限制法延缓衰老中SIRT1的作用机制进行了综述.     

延缓衰老有妙招

人的衰老是一个自然规律,但日常生活中,常可见到这样的现象,相同年龄和相同环境的人,从外表看可以相差10岁甚至更多。据调查资料显示,这是由于生活中很多小细节,也许因为不注意,但却能影响健康和容貌,以致使人提早衰老。那么,怎样能使人延缓衰老呢?专家推荐延缓衰老八妙招:妙招一,要重视早餐早餐在饮食计划中,起着决定性作     

Effect of aging and anti-aging caloric restriction on the endocrine regulation of rat liver autophagy

Autophagy is a process that sequesters and degrades altered organelles and macromolecular cytoplasmic constituents for cellular restructuring and repair, and as a source of nutrients for metabolic use in early starvation it may be involved in anti-aging mechanisms of caloric restriction. The effects of 40% daily dietary restriction (DR) and intermittent feeding (EOD) on the age-related changes in the endocrine regulation of autophagic proteolysis were studied by monitoring the rate of valine release from isolated rat liver cells. Results show that in ad libitum-fed rats sensitivity of autophagy to glucagon and insulin declines by one order of magnitude in older rats. Both DR and EOD maintain the sensitivity to glucagon at juvenile levels, whereas only EOD can fully maintain response to insulin. It is concluded that changes in the sensitivity to glucagon may have a role in the aging process.     

Early-adulthood caloric restriction is beneficial to improve renal redox status as future anti-aging strategy in rats

AimsCaloric restriction (CR) is an experimental approach proposed to alleviate age-related oxidative damage. In the present study, we investigated the consequences of CR on renal redox homeostasis in rats at a specific time frame in early-adulthood..MethodsThree groups of male Sprague-Dawley rats; young control at 6-month-old, 2-year-old subjected to 40% CR between 18^th-24^th months of age, and their non-CR controls were sacrificed, and numerous redox status biomarkers including protein oxidation, glycation, lipid peroxidation, glycation end products, thiol groups, and superoxide dismutase were assayed. It was also ensured that CR rats and their non-CR corresponding rats had similar body weights at the end of the study to decrease the confounding effects of different body weights on redox homeostasis and caloric restriction.ResultsAfter CR, the detrimental effects of the protein oxidation, glycation, and lipid peroxidation were significantly improved in the renal tissue CR rats when compared to their non-CR control group. However, there were no significant difference in thiol fractions between younger controls and both of the elderly groups.ConclusionDetrimental consequences of renal senescence on redox homeostasis are significantly improved via CR especially applied in early-adulthood.     

Lifestyle and nutrition,caloric restriction,mitochondrial health and hormones: Scientific interventions for anti-aging

Aging is a universal process to all life forms. The most current and widely accepted definition for aging in humans is that there is a progressive loss of function and energy production that is accompanied by decreasing fertility and increasing mortality with advancing age. The most obvious and commonly recognised consequence of aging and energy decline is a decrease in skeletal muscle function which affects every aspect of human life from the ability to play games, walk and run to chew, swallow and digest food. There is hence a recognised overall decline of an individuals’ fitness for the environment that they occupy. In Westernised countries this decline is gradual and the signs become mostly noticeable after the 5th decade of life and henceforth, where the individual slowly progresses to death over the next three to four decades. Given that the aging process is slow and gradual, it presents with opportunities and options that may ameliorate and improve the overall functional capacity of the organism. Small changes in function may be more amenable and likely to further slow down and possibly reverse some of the deleterious effects of aging, rather, than when the incremental changes are large. This overall effect may then translate into a significant compression of the deleterious aspects of human aging with a resultant increase in human life expectancy.     

Leptin reverses the inhibitory effect of caloric restriction on longitudinal growth

Caloric imbalance, particularly in critical periods of growth and development, is often the underlying cause of growth abnormalities. Serum levels of leptin are elevated in obesity and are low in malnutrition and malabsorption. The aim of the present study was to determine whether leptin integrates energy levels and growth in vivo, as shown previously in our ex vivo experiments, even in the presence of caloric restriction. In the first part of the study, mice were divided into three groups. Two groups were fed ad libitum and received leptin or vehicle only, and the third group was pair-fed with the group injected with leptin to dissociate leptin's effect on growth from its effect on food consumption. Mice given leptin had a significantly greater tibial length than untreated pair-fed animals and a similar tibial length as control mice fed ad libitum despite their lower weight. In addition, leptin significantly increased the overall size of the epiphyseal growth plate by 11%. On immunohistochemistry and in situ hybridization studies, leptin stimulated both the proliferation and differentiation of tibial growth plate chondrocytes without affecting the overall organization of the plate. There was also a marked increase in the expression and level of IGF-IR. In the second part of the study, two groups of mice were fed only 60% of their normal chow; one was injected with leptin, and the other was injected with vehicle alone. Caloric deprivation by itself reduced serum levels of IGF-I by 70% and the length of the tibia by 5%. Leptin treatment corrected the fasting-induced growth deficiency, but further reduced the level of serum IGF-I. These results indicate that leptin stimulates growth even in the presence of caloric restriction independently of peripheral IGF-I.     

Telomere dynamics in rhesus monkeys: no apparent effect of caloric restriction

The role of telomere attrition in limiting the replicative capacity of cells in culture is well established. In humans, epidemiologic evidence suggests telomere length (TL) in leukocytes is highly variable at birth and inversely related to age. Although calorie restriction (CR) significantly increases life span in most rodent models, its association with TL is unknown. Using linear regression analysis, TLs (as measured by Southern blot analysis) of skeletal muscle (a postmitotic tissue that largely represents early development TL), fat, leukocytes, and skin were tested for effects of age, sex, and diet in 48 control and 23 calorie restriction rhesus monkeys. After controlling for the individual's muscle mean TL, differences between leukocytes muscle and skin muscle were significantly associated with age (p = .002; p = .002) and sex (p = .003; p = .042), but not calorie restriction (p = .884; p = .766). Despite an age-dependent shortening of TL in leukocytes and skin, calorie restriction did not significantly affect TL dynamics in these samples.     

Regulation of energy intake and mechanisms of metabolic adaptation or maladaptation after caloric restriction

Reviews in Endocrine and Metabolic Disorders - Despite their critical role in susceptibility to metabolic diseases such as obesity and type 2 diabetes, mechanisms regulating energy balance are...     

An in vitro model of caloric restriction

The mechanisms underlying the ability of caloric restriction (CR) to extend life span and enhance stress responsiveness remain elusive. Progress in this area has been slow due to the complexities of using animals for CR studies and assessing life span as the measure of CR effectiveness. It is therefore of great interest to develop in vitro models of CR. Here we use sera obtained from either Fisher 344 rats or Rhesus monkeys that were fed ad libitum (AL) or CR diets to culture various cell types. We show that treatment of cultured cells with CR sera caused reduced cell proliferation, enhanced tolerance to oxidants and heat, and heightened expression of stress-response genes. These phenotypic features mirror the effects of CR in animals. Supplementation of CR serum with insulin and insulin-like growth factor (IGF)-1 partially restored the proliferative and stress-response phenotype that was seen in cells cultured with AL serum, indicating that reduced levels of insulin and IGF-1 likely contribute to the CR-related effects. This in vitro cell culture model recapitulates key in vivo proliferative and stress-response phenotypic features of CR, and further suggests that endocrine mechanisms contribute to the enhanced stress responsiveness observed in CR animals.     

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.     

Tissue-specific effect of age and caloric restriction diet on mitochondrial DNA content

The effect of age and caloric-restriction (CR) diet on mitochondrial DNA (mtDNA) content in different rat tissues was investigated. A decrease of the mtDNA content occurs with aging in liver and soleus muscle, whereas there is no age-related significant change of mtDNA content in brain. CR fully reverses the age-dependent loss of mtDNA in liver and soleus, whereas it results in a significant increase of mtDNA amount above the value of aged ad libitum fed rats in brain. These results further support the tissue-specific effect of CR, likely because of the different dependence of tissues on external nutrient uptake.