Circadian rhythms and aging; cancer and aging
A review of research articles published in 2009 that have made or will make a significant contribution to the study of aging – part 11, the last (the beginning of the article is here).
Circadian rhythms (biological clock)The amount of evidence for the existence of a relationship between the functioning of the biological clock, genes that provide signal transmission, metabolism, cancer and aging is constantly increasing [103, 104].
One of the genes that ensure the operation of the biological clock, period, increased the duration of the period of preservation of health in aging fruit flies [105]. Moreover, the mechanism of circadian control of the NAD+ utilization process carried out by the CLOCK-SIRT1 complex has been identified [106]. Interestingly, exposure to light activated MAPK (mitogen-activated kinase) in striped danio cells; at the same time, such light-dependent activation regulated the mechanism of DNA damage repair [107]. In rats, a violation of circadian rhythms induced by the change of periods of illumination and darkness accelerates aging and promotes the formation of tumors [108]. Data have also been published that the antioxidant N-acetyl-L-cysteine reduces the severity of the symptoms of premature aging in mice associated with the deficiency of the BMAL1 protein involved in the formation of circadian rhythms [109].
Cancer and agingIt is known that a low-calorie diet slows down aging and delays the development of cancer.
In 2009, data were published according to which fasting neutralizes the side effects of chemotherapy in cancer patients. It should be noted that in patients whose tumor progression could be assessed, fasting did not cancel the decrease in tumor size and tumor marker levels caused by chemotherapy [110]. In 2009, it was found that the p53 protein-mediated relationship between aging and cancer is very complex. Thus, it turned out that the ability of p53 to act as a defense against tumor progression depends on age [111]. Moreover, earlier Levine et al. demonstrated that the activity of p53 decreases with age, and the results of a recent study indicate that the transcriptional activity of p53 is reduced in cells in the phase of physiological aging [112]. It is also interesting that transgenic mice without functional SIRT1, whose life expectancy does not increase when kept on a low-calorie diet, are characterized by a normal incidence of skin cancer, but the ability of the SIRT1 activator resveratrol to prevent the development of cancer in such animals is significantly reduced [113]. This indicates that the antitumor activity of resveratrol is at least partially mediated by SIRT1.
A decrease in the frequency and delayed occurrence of fatal neoplastic diseases is characteristic of transgenic mice that do not have a functional receptor (binding protein) for growth hormone. These changes are similar to the effects observed when keeping animals on a low-calorie diet, and, accordingly, may be the main factor contributing to the increased life expectancy of such animals [114].
In general, 2009 was very fruitful in terms of deepening our knowledge about the mechanisms of aging and its relationship with age-related diseases, as well as the development of promising strategies and drugs for pharmacological interventions in the aging process. When used in combination with drugs and diet, some approaches can slow down the aging process, but its complete prevention is impossible [115].
The list of references to the article “Impact papers on aging in 2009" is given in a separate file.
Portal "Eternal youth" http://vechnayamolodost.ru28.09.2011