How to check "pills for old age": age–related diseases - a marker of aging
Checking the effectiveness of aging-slowing drugs by treating age-related diseases (Part 1).
Article by Mikhail V. Blagosklonny Validation of anti-aging drugs by treating age-related diseases
published in Aging magazine, March 2009, volume 1, No. 3.
Translated by Evgenia Ryabtseva.
Summary:
People die from age-related diseases, which are fatal manifestations of the aging process. To increase life expectancy, aging-retarding drugs should delay the development of these diseases. The combination of age-related diseases is an optimal biomarker of aging. If the drug is used to treat one of the chronic diseases, its effect on other diseases (atherosclerosis, cancer, prostatic hyperplasia, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-associated macular degeneration) can be evaluated in the same group of patients. If this group is large enough, the aging-slowing effects can be assessed within a few years. Surprisingly, the results of a retrospective analysis of clinical and preclinical data demonstrate the existence of four possible approaches to combating aging.
ProblemThe existence of aging-slowing drugs no longer belongs to the realm of fiction.
Numerous genes have been identified in the genomes of various organisms that determine the nature of aging and longevity and indicate the intended targets of potential drugs that can slow down aging. However, how to apply an aging-slowing drug to a person? There are two problems. Firstly, it may take almost a lifetime to determine the effect of aging-slowing agents on the aging process of a person [1]. Secondly, at first glance, it is obvious that it is desirable to test aging-slowing drugs on healthy people. However, all drugs have undesirable side effects. The possibility of side effects makes it almost impossible to conduct clinical trials involving healthy individuals. How can these problems be solved? How can we evaluate the effectiveness of aging-slowing drugs without conducting life-long clinical trials involving healthy individuals?
DecisionThe solution involves two stages.
First, we need to find an indication for taking the drug as a therapy for at least one chronic disease. After that, the drug can be tested with the participation of people, but not as a drug to slow down aging, but as a means to treat a certain disease. In fact, this approach was proposed for the introduction of sirtuin activators into clinical practice [2, 3].
Secondly, we need to find a biomarker of aging, which is an absolute prognostic factor of longevity. After that, the aging-slowing effect of the drug can be evaluated using this biomarker on the same patient population.
Aging and age-related diseasesAging can be defined as an increase in the probability of death.
This allows you to estimate the rate of aging. People do not die as a result of "healthy" aging, but because of age-related diseases. Healthy aging (late onset of the disease stage) is associated with longevity. For example, people who have reached the age of 100 are characterized by a late onset of age-related diseases, including diseases of the cardiovascular system, type 2 diabetes, cancer and Alzheimer's disease. In other words, long-living people are distinguished by good health and vice versa [4, 5]. Given that, by definition, all age-related diseases are associated with aging, these diseases are interrelated with each other. In fact, people often suffer from several diseases at the same time: diabetes, atherosclerosis, hypertension, macular degeneration, hyperplasia and prostate cancer (in men) or breast cancer (in women), Alzheimer's disease and osteoarthritis. Therefore, the elimination of one disease (for example, cancer) will not significantly increase the maximum life expectancy of a person. According to statistical calculations, "complete elimination of Alzheimer's disease would increase the average life expectancy by about 19 days" [6]. However, if the drug delays or stops the development of all diseases, a person's life expectancy should increase. Otherwise, what can cause death if all causes are eliminated? Given that human longevity is limited by death from age-related diseases, a drug that really slows down aging should delay the development of these diseases. In other words, if the drug does not delay the development of age-related diseases, it cannot increase life expectancy. Conversely, if the drug prevents the development of age-related diseases, it should increase life expectancy.
Biomarker of aging of the bodyConsidering that (a) an increase in the probability of death is an indicator of aging and that (b) the mortality rate is determined by the totality of all diseases, we can conclude that the optimal biomarker of aging is the totality of all age-related diseases.
Any single age-related disease is not a biomarker of aging, since the development of a certain disease is caused by many factors. For example, smoking increases the risk of lung cancer, but not Parkinson's disease. However, aging is a risk factor for both diseases. At the same time, even with regard to lung cancer, aging is a more significant risk factor than smoking. Aging is the most significant risk factor for all age-related diseases. Regardless of whether the same mechanism underlies aging and the development of the disease, or aging simply aggravates the predisposition to the disease, in any case, the suppression of the aging process will delay the development of diseases, thus increasing life expectancy.
Continuation: Drugs that slow down aging.
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07.11.2011