Calorie Restriction - Term Paper Example

Calorie restriction and lifespan Aging is a naturally occurring process that is visible in most of the living species including humans and is the forerunner to the eventual demise of those living species. Thus, ageing is the progressive loss of both physical and mental functions in humans, resulting in decreasing functionality, productivity, fertility, etc and in turn resulting in increasing mortality. (Kirkwood and Austad 2000). Although, ageing is a common phenomenon to the humans since their ‘origination’, the process of ageing has been slowed down from the middle of the last century. Due to optimal advances in health practices and technology, the average life span of people all over the world particularly in developed countries, has greatly increased. To further delay the process of aging and live longer, various health practices are carried out all over the world. Although, there are many of these practices, only few are systemized and supported by actual and genuine trials done by experts, which can stand scrutiny from any quarters. One of the main age delaying practices which has been studied extensively and intensively is calorie restriction. Background Calorie restriction (CR) is a lifestyle choice or a dietary schedule or experimental protocol in which the total intake of calories through food are restricted, with the restriction levels based on the subject’s previous calorie intake levels. This dietary regime is consciously or unconsciously practiced by various people and importantly implemented among other living species as test subjects in labs. The scientific studies to find the correlation between restricted diets and ageing delay was started in the first half of the 19th century. It was in 1935, the effect of food restriction on ageing or life span in laboratory rats was first described by Clive M. McCay and his colleagues at Cornell University. By placing rats on a very low calorie diet, Clive M. McCay and his team extended the outer limit of the animals’ life span by 33 percent, from three years to four. “They subsequently found that rats on low-calorie diets stayed youthful longer and suffered fewer late-life diseases than did their normally fed counterparts.” (Weindurch 2006, p. 54). Since then, CR has been regarded as a key intervention which can slow aging in many living species particularly rodents. Another trial using monkeys, which has more common genetic content with humans, has been underway and it is also showing the correlation between CR and ageing. The key thing about these trials is that CR does not mean malnourishment because they receive enough protein, fat, vitamins and minerals to maintain efficient operation of their tissues. With these trials in the right direction, the key question is can the relation between CR and ageing process is relevant or applicable to humans. As any study related to human ageing would need longer period of study, extending from early ages till the death of the subjects, researchers are trying to find whether animal results are also applicable to humans. Without doing any direct trials on humans, researchers are trying to find how CR impacts human lifespan by focusing on certain age related mechanisms Mechanisms Mitochondrial mechanisms Inside the animal subjects, certain mechanisms or processes takes place due to CR and researchers feel that those processes would also be happening in the humans and thereby could delay the ageing process. The view or mechanism that has so far garnered the most convincing support is that calorie restriction extends survival and vitality primarily by limiting injury of mitochondria by free radicals. (Rose 2004, p. 25). Free radicals, the highly reactive molecules, are maximally produced in mitochondria, and quite paradoxically it is one of the hardest hit sites. With constant hits by the radicals, the ‘injured’ mitochondria’s functioning deteriorates, and thus the fight against diseases and other age related complications also gets affected. However, the researchers opine that CR will reduce the formation of free radicals and in turn could delay ageing. That is, the mitochondrial machinery, which play a role in producing energy for the cells and thereby the human body, also produces most of the free radicals in cells as a by-product. One such by-product is the superoxide radical (O2.–) and it can be further converted into an extremely aggressive hydroxyl free radical (OH.–). These radicals can damage proteins and lipids in the tissues as well as DNA anywhere in the cell, with mitochondria being the most vulnerable. “Presumably they are at risk in part because they reside at or near the “ground zero” site of free-radical generation and so are constantly bombarded by the oxidizing agents.” (Weindurch 2006, p. 59). With mitochondrial DNA lacking the protein shield to protect from radicals and also with free radicals attacking other cellular components outside the mitochondria, there is further impairing of cell functioning. As cells become less efficient, the tissues and the organs, which they compose, also becomes weaker and with that body reaches a state where it cannot the challenge the vagaries of ageing. “Conversely, oxidative damage to key genes and proteins may result in a significant decrement in the efficiency of cell functioning.” (Merry 2004, p.8). Although, cells possess antioxidant enzymes that can detoxify free radicals and reduce its negative impacts, it is not foolproof and as effective, thus leading to aging. Free radicals have been suspected of contributing to aging since the 1950s, when Denham Harman of the University of Nebraska Medical School suggested that their generation in the course of normal metabolism gradually disrupts cells. (Weindurch 2006, p. 57). This being the case researchers doing animal trials, state that CR has shown to reduce free radicals formation, thereby keeping mitochondria in an optimal state, thus enabling it to protect the body from the ageing process. Rajindar S. Sohal of the University of Southern California, William C. Orr of Southern Methodist University and their colleagues have provided evidences of how CR by particularly controlling OH.– radicals slows oxidative injuries to the mitochondria and thereby retards ageing. “When the workers looked at mitochondria harvested from the brain, heart and kidney of mice, they discovered that the levels of the superoxide radical and of hydrogen peroxide were markedly lower in animals subjected to long-term calorie restriction than in normally fed controls.” (Weindurch 2006, p. 59). Studies indicate that calorie control may minimize free-radical generation in mitochondria by reducing levels of a circulating thyroid hormone known as triiodothyronine, or T3, through unknown mechanisms. Although, many studies verified the role of CR in containing free radicals and delaying the ageing process, there appears to be some inconsistencies. For example, in the study of Chung et al (1992), 1.5 months after the initiation of CR feeding, a significant reduction in the concentration of free radical, 8-hydroxy--deoxyguanosine (8-OHdg) was observed in rat liver, however, a later study using the same strain of rat could not confirm these early effects of CR feeding in attenuating oxidative damage in genomic DNA. (Merry 2004, p. 7). This lack of consistency regarding DNA oxidative damage as a function of age shows that although it has been verified that CR slows the ageing process, there are some unanswered questions. As there are two sides to this issue and importantly as there are certain inconsistencies regarding CR’s ability to control ageing in a consistent and continuous manner, there are some loose ends. Bodily mechanisms Apart from this key mechanism, there are also several other mechanisms, which directly implicates how CR can control various complications of ageing as well as the complications which leads to ageing. One of the main aspects, which is visible in animals and which can be replicable in humans as well, is the maximal decrease in various diseases and other infections among CR introduced subjects. “Beyond altering survival, low-calorie diets in rodents have postponed most major diseases that are common late in life including cancers of the breast, prostate, immune system and gastrointestinal tract” (Weindurch 2006, p. 55). As the chances of getting these diseases are reduced considerably among the CR subjects, their body will remain stronger and will continue to function optimally, thereby remaining youthful. That is, with minimal to no diseases, all the body machineries will be focused on cutting down the factors which causes ageing. Another hypothesis regarding the relation between CR and minimization of cancer is that CR slows the rate of cell division in many tissues. As uncontrolled proliferation of cells is a hallmark of cancer, thus changing to slower cell division could potentially explain why the incidence of several late-life cancers is reduced in animals fed low-calorie diets. Along with this, there are certain other related mechanisms, which exhibits that ageing can e delayed is seen in CR related subjects. For example, the subjects appear to have a general up-regulation of mechanisms protecting against accumulation of somatic damage, also there is a optimal Protein and serum corticosteroids turnover, plus there is increased DNA repair activity, thus slowing the ageing process and increasing the lifespan. (Kirkwood and Shanley, 2005). The key age related mechanism which is also influenced by CR is the immunity of the subjects. That is, according to various studies, CR does allow the immune system to deteriorate and thus keeps the body optimal to fight all complications, thereby extending the life span. Certain immune responses decrease in normal mice at one year of age (middle age) but do not decline in slimmer but genetically identical mice until age two. Calorie restriction virtually eliminates the development of autoimmune diseases in susceptible strains of mice (Weindruch and Sohal, 1997). Reproductive mechanisms The other mechanism, influenced by CR and which indirectly influences ageing and leads to longer life spans, is the reproduction process of the subjects. That is, during CR, the energy is minimally spent on reproduction process, while maximally spending on the protection of bodily functions. For example, normal rodents typically invest a large fraction of their energy budget in reproduction, however the CR introduced rodents temporarily reduce reproductive activity, because not only is reproduction costly in direct physiological terms but behaviours associated with reproduction can also be expensive. Thus, when it comes to survival or (sex) reproduction, subjects appears to be selecting survival, by spending their ‘resources’ to protect their body, thereby leading to an extended lifespan. Food restriction results in animals becoming infertile, with calorie restriction in female mice leading to 40% arrests in follicular cycles in females. This correlation between sexual reproduction and the ageing process in the animal subjects is also visible in humans. Although, no scientific study was done regarding this correlation, certain bodily functions and natural occurrences justify the concept that abstinence from reproduction activities indirectly results in longer lifespan. As stated by Rose (2004), aging mainly arises in sexually reproducing species because the force of natural selection declines after the start of adulthood. In contrast to deleterious genes that act early, those that sap vitality in later years would be expected to accumulate quite quickly, leading to ageing. This correlation between reproduction and delayed aging is clearly visible during the naturally occurring CR related event of famine. During periods of famine, “the primary role of the food restriction response is to shift resources away from reproduction, and invest as much of the resultant saving as possible into increased somatic maintenance.” (Kirkwood and Shanley, 2005, p. 1012). This increased somatic maintenance during CR phase can prolong the lifespan, thus proving that CR impacts on humans ageing. Limitations and Problems The main limitation with these studies and their results being replicated for humans are that it has to be a long-term study. The ageing process in humans is not time specific and would take a longer time, and so researchers has to follow the subject for a long time, to come to conclusions. “To be most informative, such investigations would have to follow subjects for many years—an expensive and logistically difficult undertaking.” (Weindurch 2006, p. 56). Because of this major limitation, CR on humans has not been studied by any research group in a full-pledged manner. As, CR trials in humans would take a long time necessitating more than one group and also as there are doubts whether the subjects would cooperate or participate for such a long time, there are clear skepticisms whether all the above discussed ageing related mechanism would work and will be replicable in humans. Diet restriction works in rodents but has not been studied systematically in humans and is not practical for most people. (Rose 2004). With evidences regarding CR’s impact on humans, non-existent, it would be difficult to fully confirm that CR can extend human lifespan. So, the common view among the scientific circles is that it would take many more years of research and studies with human subjects to come to conclusions regarding CR’s impact on humans. “It may take another 10 or 20 years before scientists have a firm idea of whether calorie restriction can be as beneficial for humans as it clearly is for rats, mice and a variety of other creatures.” (Weindurch 2006, p. 60). Thus, it has been clearly shown that although results from the animal trials are quite replicable among the humans, some more research need to be done. The other limitation is that it would be difficult for the researchers to find a set point for each human subject, basing on which the calorie has to be lessened by 10 to 25 percent from that point. The set point can be described as the minimum weight the body is “programmed” to sustain, if he/she does not eat in response to external stimulus. To test human subjects, researchers have to lessen the calorie level by 10 to 25 percent of that set point. However, the problem with this guideline is that determining an individual’s set point is difficult and tricky. (Weindurch 2006, p. 60). So, when the researchers involve humans, it would be better if they are engaged in form of trial and error to find the calorie level, which can reduce the blood glucose or cholesterol level. Although CR in animals has so far lead to visible signs regarding extended lifespan, there is skepticism whether it could also lead to other bodily complications. That is, studies done by various groups, shows that a subject put under CR could develop various problems ranging from infertility to osteoporosis, apart from the mental stress that could happen because of the restriction in food consumption. According to Weindurch (2006) a prolonged anovulatory state, if accompanied by a diminution of estrogen production, might increase the risk of osteoporosis (bone loss). Another key problem associated with CR is that the body could become weak physically and this will make the body susceptible to various diseases. It is a high possibility that continued CR would weaken and compromise individuals’ ability to withstand stress, such as injury, infection or exposure to extreme temperatures. Although, these problems as a result of CR were a high possibility, stress resistance has been little studied in rodents on low-calorie diets (Weindurch 2006, p. 60). Conclusion From the above analysis, it is clear that Calorie Restriction is having or could have an impact in respect to the lifespan of the humans. The initial experiments with the animals have shown that it is possible to extend the lifespan through CR. The results and the mechanisms that happen inside the animal under CR could be visible among humans as well. Importantly, the mechanisms which controls ageing in humans has high probabilities of being controlled by CR. However, there are certain limitations in coming to these conclusions, because certain logical, financial and even social impediments (humans have a poor track record adhering to severe diets) has to be crossed to conduct a full-pledged human trials and test the hypothesis. However, with various ageing mechanisms in human body happening under the influence of calorie intake, CR could impact and extend or even maximize the lifespan of humans. References Kirkwood, TBL and Austad, SN 2000, Why do we age? Nature, vol. 408, pp. 233-238 Kirkwood, TBL and Shanley, DP 2005, Food restriction, evolution and ageing, Mechanisms of Ageing and Development 126, pp.1011–1016 Merry, BJ 2004, Oxidative stress and mitochondrial function with aging--the effects of calorie restriction, Aging Cell, vol. 3, no. 1, pp. 7-12. Rose, MR 2004, Will human aging be postponed? Scientific American INc Weindruch, R 2006, Calorie Restriction and Aging, Scientific American INc Weindruch, R and Sohal, RS 1997, Caloric intake and aging, New England Journal of Medicine, vol. 337, pp.986–994. Read More