Life-extension drugs

Life-extension drugs



Calorie restriction and fasting helps to prevent cancer and tumours

Researchers at University Of Alabama at Birmingham have shown that calorie restricted diets specifically restriction in glucose can help human beings by increasing the life of cells. The finding is published online in FASEB journal which can lead to restriction of aging and prevention of cancer. Such type of calorie restriction can also lead to control of age related diseases. To carry out this study, researchers used human lung cells and precancerous human lung cells that were at the beginning of cancer development. The cells were grown under laboratory environment and were given normal or reduced level glucose. After a period of few weeks, researchers found that normal cells lived longer and many of the precancerous cells died when given less glucose. The reduced level of glucose causes higher activity of gene that formulates the level of telomerase which is an enzyme that extends life span.

In another study carried out by researchers at University Of Texas at Austin and University Of Texas M.D. Anderson Cancer Centre have revealed that restriction in calorie diet and prevention of weight gain reduce the development of pancreatic lesions that leads to cancer. The research clearly indicates the relation between calories restricted diets, an overweight diet and pancreatic cancer. The study was carried out on mice that were having pancreatic abrasion leading to cancer. The findings from the study indicate that calorie restriction hinders the development of pancreatic tumours caused by chronic inflammation and obesity. The analysis of the study leads to connection between calorie intake and a protein known by the name of Insulin like Growth Factor (IGF)-1. It is believed that calorie restriction decreases levels of IGF-1 which is an important growth factor of cancer cells. The mice on heavier diets showed more and bulky lesions as compared to those on restricted diet. The lesions continuously developed were associated with pancreatitis-inflammation of the pancreas which further enhances into pancreatic cancer causing their death.

The diet given to calorie restricted group of mice was 30% lower in calories than the overweight group and 50% lower than the obese group. Out of the total subjects, only 7.5 percent of mice on calorie restriction diet developed pancreatic lesions with no symptoms of illness. In overweight diet group, 45 percent of mice showed the development of pancreatic lesions while 57.5 percent of mice in obese group developed larger and bulky pancreatic lesions.

Almost a century ago Moreschi and Rous published their observations on the beneficial impact of calorie restriction on transplanted and induced tumours of cancer. In the year 1940, researchers at the laboratories of Tannenbaum at Chicago and Baumann at Wiscosin developed the design of studies and showed that the observation of restricted tumour was due to low calorie intake diet. Energy restriction enhances DNA repair and moderates oxidative damage to DNA. Calorie restricted diet also effects insulin metabolism and gene expression. The increase of cancer with increase in age is well known and many theories and metabolism are proposed till today to prevent or restrict it. The importance of nutrition in delaying aging and preventing cancer is very well recognized and is said to be one of the most useful theories against cancer. Calorie restriction diet when given to animals shows reduction in oxidative stress and effective increase in life span along with the prevention of cancer due to diminished mitogenesis. Inadequate diet and deficiency of folic acid along with impaired DNA methylation status are associated with increased cancer risk. Other well known dietary strategies against cancer include fibre intake with more amount of fruits and vegetables. Physical activity on daily basis also contribute to reduction is cancer risk.

Researchers at Department of Obstetrics and Gynaecology, Mount Sinai Hospital Medical Centre at Chicago studied the dietary restrictions on three to four months old tumour free and tumour bearing fisher rats. The subjects were given proper diet every alternate day followed by fasting at alternate day. The unrestricted diet group subjects were given pleasure food every day. Sis tumour free rats on diet control at every alternate day showed the reduction in weight at rate of 2%-3% within thirteen days while the subjects on uncontrolled diet showed increase in weight of 6%-7% in fifteen days. Sixteen out of twenty four (66.7%) diet control tumour bearing rats and five out of twenty four (20.8%) diet unrestricted tumour bearing rats survived for nine days after tumour inoculation (p less than 0.005). Twelve out of twenty four (50%) diet restricted tumour bearing rats and three out of twenty four (12.5%) diet unrestricted tumour bearing rats survived for ten days after tumour inoculation (p less than 0.025). This shows that survival of tumour bearing rats was enhanced by relatively mild dietary control.

This kind of short term dietary control strategy should be included in clinical trials designed to inhibit cancer growth and to increase the life span of cancer patients. The trials and study reported to prevent cancer were designed to determine (1) the effect of calorie restriction to inhibit mammary carcinogenesis (2) the advancement of pre malignant stages to malignant is restricted by implementing dietary control (3) to explore the effects of calorie restriction on adrenal function. Mammary carcinogenesis was induced in female Sprague-dawley rats by the administration of 1-methyl-1-nitrosourea (50 mg/kg body weight) at 21 days of age. Rats were used for the study in which they were divided among the groups of dietary supplements ranging from low calorie diet to pleasure food and were inspected for detection of mammary tumours. The urine was collected at regular intervals for 35 days and was analysed for corticosterone by direct radioimmunoassay. Calorie restriction resulted in latency of palpable carcinomas and reduction in mammary cancer. The percentage of pre malignant mammary lesions increased with increase in degree of calorie restriction where as the percentage of carcinomas decreases.

Poison regression analyses and level of caloric restriction along with urinary cortical steroid excretion were performed. The analyses indicated that urinary cortical steroid excretion was an independent predictor in response of animal carcinogenesis response. The final output of the study showed the use of short term dietary control to prevent mammary carcinogenesis and progression of pre malignant to malignant cells. It also indicated the feasibility of identifying protective effect of calorie restriction which is independent of energy restriction and increases the possibility of to tackle the practical problems of implementing dietary control strategy in human population.

At department of Hygiene, Akita University School of medicine the investigation was carried on the influence of dietary restriction on pituitary ovarian axis and on gene expression of mouse mammary tumour virus. The subjects include F1 females from the mating of SHN female and C3H male mice as these hybrids shows high incidence of mammary tumours. The mice were kept on calorie restricted diet for three weeks (50 kcal / week) or on control diet for five weeks (95 kcal / week). The reference for this used were three C57BL/6J Jcl pleasure food fed female mice having eight age of eight weeks. The mean cellular contents of prolactin and growth hormone in pituitary were found to be reduced in mice raised on calorie restriction diet. This was accompanied by decrease in number of lactrotrophs while the decrease in growth hormone was not accompanied by decrease in somatotrophs.

Both control diet group and reference mice showed two or three corpora lutea (temporary endocrine structure in mammals which in involved in production of estrogens and progestogens) per ovarian section. The decrease in mammary tumour virus was investigated by electron microscopy to confirm the validity of experimental conditions. The mammary tumour viruses were rarely found in dietary controlled mice and reference subjects. The development of mammary glands as indicated by number of rough endoplasmic reticulum was delayed in dietary controlled mice. Thus it was clear from the study that calorie restriction inhibits ovulation, decreases number of lactrotrophs and delays mammary gland development.

The reduction of nutritional energy intake reduces the incidence of cancer in humans and experimental animals. It is recommended to start the dietary control before the carcinogen is induced with intense effort and should last a long time. The control on diet depends on strain, sex and age of subjects. The dietary control strategy may influence the immuno-surveillance, change the hormonal equilibrium or can alter the activities of enzymes involved in carcinogen metabolism. Since over eating and obesity increases the risk of cancer, it is better to follow calorie restriction diet which is the cheapest and most effective way to prevent cancer.

Marc Hellerstein, professor of human nutrition in the Department of Nutritional Sciences and Toxicology at UC Berkeley’s College of Natural Resources said that cell proliferation is the real key to fight against the cancer disease. Cancer is the uncontrolled division of cells caused by the presence of multiple mutations. Scientists have been certain only of a link between calorie restriction and reduction in the rate of cell proliferation. Studies over the past 70 years have shown that diet restriction not only helps to reduce cell proliferation but also extends the life span. It is believed that physical exercise and dietary control can prevent premature death due to aging diseases, enhances insulin sensitivity and lowers the risk of heart disease. Several trials were conducted with control group of mice that were given five percent fewer calories and were fed three times a week. These subjects were compared with group that were given thirty three percent lower calories. The trial period ranges from two weeks to three months. Researchers found that thirty three percent restricted diet group showed significant decline in profile ration rates for skin, breast and lymphocyte cells.

In all cases the division rates for breast cells were reduced the most. Mice with lowest calorie diet had breast cell proliferation that were only 11 percent of those for control group while mice fed intermittently showed breast cell proliferation of 37 percent of those for the control group. Further analyses reveal that the estruses cycle stopped for mice on the lowest calorie diet while the mice on intermittent diet showed the regularity of cycles. The researchers also found out that the weight lost during the calorie restriction period was regain after starting the normal diet. Scientific evidence also indicates that eating can also impact mental state and emotions. The UC Berkeley study is the first to throw light for calorie restriction impact on cell division. The researchers used heavy water for their study which is identical to normal water but is about 10 percent heavier because of an extra neutron. As heavy water is incorporated into the DNA of new cells, researchers were able to compare the mass of DNA from tissues in experimental animals to tissues from control animals. This helps significantly to researchers for accurately gauging the effects of relatively small changes in diet.

Moreschi C (1909) Bezeihungen zwischen Erhanburg und Tumorwachstum. Zeitschrift fur Immunitatsforsch 2:661-675
Rous P (1914). The influence of diet on transplanted and spontaneous tumour. J Exp Med 20:443-451
Tannenbaum A. The initiation and growth of tumours. Introduction, effects of under feeding.
Dietary restriction, tumours and aging in rodents; J Gerontol. 1989 Nov; 44(6): 67-71
Mech Aging Dev. 1980 Aug; 49(2):93-104 Koizumi A, Masuda H, Wada Y, Tsukada M, Kawamura K, Kamiyama S, Walfrod RL.
Bartke A, Masternak MM, Al-Regaiey KA, Bonkowski MS (2007). Effects of dietary restriction on the expression of insulin-signalling-related genes in long lived mutant mice.
Role of calories and calorie restriction in carcinogenesis. Hematol Oncol Clin North Am. 1991 Feb; 5(1): 79-89.

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