The influence of genes on life expectancy: detailed review
1. Genetics of longevity: fundamental principles
Longevity, or exceptional life expectancy, is a complex sign determined by the interaction of genetic, environmental and behavioral factors. Although the influence of the lifestyle and the environment is undeniable, the growing amount of data indicates a significant role of genes in determining the potential life expectancy of a person. The study of longevity genetics is focused on the identification of genes and genetic options that either directly contribute to an increase in life expectancy, or affect the diseases and aging processes associated with age.
1.1. Longevity inheritance:
Assessment of inheritance of longevity is an important first step in understanding genetic influence. Studies of the twins showed that the inheritance of life expectancy in humans varies, but, as a rule, ranges from 15% to 30%. This means that approximately 15-30% of variations in life expectancy between people can be explained by genetic factors, while the rest falls on the share of environmental factors and random events. It is important to note that these estimates of inheritance can vary depending on the population, age and research methodology.
1.2. Longevity inheritance models:
Models of inheritance of longevity are not always simple and linear. Unlike monogenic diseases caused by mutations in one gene, longevity is probably a polygenic sign determined by a combination of many genes, each of which makes a short contribution. These genes can interact with each other (Epistasis) and with environmental factors (the interaction of the gene-environment), which further complicates the picture. Some researchers suggest that longevity may be associated with the presence of favorable alleles in several genes, while others emphasize the importance of genes that protect against age -related diseases.
1.3. Genetic heterogeneity of longevity:
It is important to recognize the genetic heterogeneity of longevity. This means that genetic factors contributing to longevity can vary between different people and populations. For example, genetic options that contribute to longevity in one population may not have the same effect in another population due to differences in a genetic background, environment and lifestyle. This emphasizes the need to conduct research in various populations to obtain a more complete idea of the genetics of longevity.
2. Key genes and genetic options associated with longevity
Despite the complexity of longevity genetics, studies have revealed a number of genes and genetic options, which, as it was shown, are associated with an increase in life expectancy and/or a decrease in the risk of age -related diseases. These genes are involved in various biological processes, including:
2.1. Apoe (Apolipoprotein E):
The APOE gene encodes a protein that plays the role in the transport of cholesterol and lipids in the blood. There are three main APOE alleles: ε2, ε3 and ε4. The APOE ε4 allele is associated with an increased risk of developing Alzheimer’s disease and cardiovascular diseases, which, in turn, can reduce life expectancy. On the contrary, the APOE ε2 allele is associated with the lower risk of these diseases and can help increase life expectancy. The mechanism of action of APOE in relation to longevity is likely to be associated with its role in maintaining lipid homeostasis and protecting from neurodegeneration.
2.2. FOXO3 (Forkhead Box O3):
The Foxo3 gene is part of the Foxo transcription factors that play an important role in the regulation of cellular stress, metabolism, immunity and DNA reparations. Studies have shown that certain Foxo3 options are associated with an increase in life expectancy in humans, as well as in various model organisms, such as worms and flies. The mechanisms with which Foxo3 contributes to longevity include activation of genes involved in protection against oxidative stress, autophagy (cell treatment process) and regulation of insulin/IGF-1 levels.
2.3. SIRT1 (Sirtuin 1):
Sirtuin genes encode the family of proteins with deacecilasis activity and participating in the regulation of aging and metabolism. Sirt1 is the most studied sirtuin, and studies have shown that it plays a role in improving sensitivity to insulin, protecting from oxidative stress and maintaining the stability of the genome. Activation of SIRT1 with the help of calorie restrictions or resveratrol (polyphenol contained in red wine) is associated with an increase in life expectancy in some model organisms, although the influence on human life expectancy is still studied.
2.4. CETP (Cholesteryl Ester Transfer Protein):
The Cetp gene encodes a protein that is involved in cholesterol transport between lipoproteins in the blood. Some CETP options are associated with a higher level of HDL cholesterol (“good cholesterol”) and a lower risk of cardiovascular disease. Studies have shown that certain CETP options are associated with an increase in life expectancy, especially in women.
2.5. CDKN2A/INK4A (Cyclin-Dependent Kinase Inhibitor 2A):
The CDKN2A/Ink4A gene encodes a protein, which is an inhibitor of cyclin-dependent kinaz participating in the regulation of the cell cycle. The increased expression of CDKN2A/Ink4A is associated with cell aging, which plays a role in the pathogenesis of age diseases. However, studies have shown that certain options for CDKN2A/Ink4A can be associated with an increase in life expectancy, probably by regulating cellular aging and preventing uncontrolled cell proliferation.
2.6. mTOR (mammalian Target of Rapamycin):
MTOR is Serin/TROONIN KINAZ, which is a central regulator of cellular growth, metabolism and autophagy. Dysregulation of MTOR is associated with age -related diseases, such as cancer, diabetes and neurodegenerative diseases. Inhibition of MTOR using rapeamycin, the medicine used to prevent organs after transplantation, it was shown that it increases life expectancy in various model organisms. Although the influence of MTOR inhibiting on human life is still studied, it is a promising field of research.
2.7. TER (Telomerase RNA Component) и TERT (Telomerase Reverse Transcriptase):
Telomeres are protective caps at the ends of the chromosomes, which shorten with each cell division. When the telomeres become too short, the cells stop sharing and enter into a state of cell aging or apoptosis (programmable cell death). Telomerase is an enzyme that can lengthen telomeres and, thus, extend the life of the cell. Ter and Tert genes encode telomerase components. Studies have shown that certain variants of these genes are associated with a larger telomere length and an increase in life expectancy.
2.8. HLA (Human Leukocyte Antigen):
HLA genes encode proteins that play an important role in the immune system. Certain HLA options are associated with increased susceptibility to autoimmune diseases, while other options can provide protection against infectious diseases. Studies have shown that certain HLA options are associated with an increase in life expectancy, probably due to the optimization of the immune response and protection against age -related diseases.
2.9. Genomic stability and DNA reparation:
The accumulation of DNA damage is one of the main signs of aging. Genes involved in DNA reparations, such as BRCA1, BRCA2 and ATM, play an important role in maintaining genomic stability and protecting against age -related diseases. Certain variants of these genes can be associated with an increase in life expectancy, probably by increasing the effectiveness of DNA reparation and reducing the risk of cancer.
2.10. Metabolism and regulation of insulin/IGF-1:
Genes involved in the metabolism and regulation of insulin/IGF-1, such as INS (insulin), IGF1R (receptor of an insulin-like growth factor 1) and IRS1 (substrate of insulin receptor 1), play an important role in aging and longevity. A decrease in insulin alarm/IGF-1 has shown that it increases life expectancy in various model organisms. Certain options for these genes can be associated with an increase in life expectancy, probably by improving sensitivity to insulin and reducing the risk of diabetes and other metabolic diseases.
3. Methods of study of longevity genetics
Studies of longevity genetics use various methodologies to identify genes and genetic options associated with life expectancy. These methods include:
3.1. Association studies throughout the genome (GWAS):
GWAS is an approach based on the analysis of the genome, which includes scanning of a large number of people to determine the genetic options (one -unique polymorphism or SNPS), which are associated with a certain sign, such as life expectancy. GWAS can help identify new genes and genetic areas that have not been previously associated with longevity.
3.2. Continuity studies:
Linkage analysis studies are used to identify chromosomal regions that will co-saber with a sign in families. This method is especially useful for studying rare genetic options that have a great influence on life expectancy.
3.3. Sequencing of the entire exom and genome:
Sequencing of the entire exom (WES) and the entire genome (WGS) are methods that allow you to determine the sequence of all genes or the entire human genome, respectively. These methods can help identify rare and new genetic options that are associated with longevity.
3.4. Research of candidate genes:
Studies of candidate genes (Candidate Gene Studies) are focused on the study of genes, which, as you know, are involved in biological processes associated with aging and longevity. This method includes an analysis of genetic options in these genes and an assessment of their association with life expectancy.
3.5. Meta-analysis:
Meta-analysis (META-ANALYSIS) is a statistical method that combines the results of several studies to increase statistical power and obtain more accurate assessments of the effects of genetic options for life expectancy.
3.6. Research on model organisms:
Research on model organisms, such as worms (C. Elegans), flies (Drosophila melanogaster) and mice, are a valuable tool for studying longevity genetics. These organisms have a shorter life expectancy than in humans, which allows experiments and study the genetic mechanisms of aging and longevity in relatively short time.
4. Interaction of the gene environment in longevity
It is important to emphasize that genes are not the only determinants of life expectancy. Environmental factors, such as diet, physical exercises, smoking, alcohol use and the effects of toxins, also play an important role. The interaction of the gene environment refers to how genetic factors can affect human sensitivity to environmental factors and vice versa.
For example, a person with a genetic predisposition to cardiovascular diseases can reduce his risk by accepting a healthy lifestyle, including a healthy diet and regular physical exercises. On the other hand, a person without a genetic predisposition to cardiovascular diseases can still get sick if he leads an unhealthy lifestyle.
The study of the interaction of the gene environment is important for the development of effective strategies for the prevention and treatment of age-related diseases and increase life expectancy.
5. Genetics of longevity in different populations
It is important to consider the genetic heterogeneity of longevity in different populations. Genetic options that contribute to longevity in one population may not have the same effect in another population due to differences in a genetic background, environment and lifestyle.
For example, studies have shown that certain genetic options associated with longevity in European populations are not associated with longevity in Asian populations. This emphasizes the need to conduct research in various populations to obtain a more complete idea of the genetics of longevity.
In addition, some populations, such as residents of Blue Zones (the regions of the world, where people live longer and healthier than on average), can have unique genetic characteristics that contribute to their longevity. The study of longevity genetics in these populations can provide valuable information about genetic factors that contribute to healthy aging.
6. Ethical and social aspects of longevity genetics
The study of longevity genetics raises important ethical and social issues that must be taken into account.
6.1. Genetic testing for longevity:
The development of genetic tests for predicting the life expectancy or risk of developing age diseases can have significant consequences. On the one hand, these tests can help people make more reasonable decisions about their lifestyle and preventive measures. On the other hand, they can lead to genetic discrimination in insurance, employment and other areas of life.
6.2. Increase in life expectancy and justice:
The development of interventions aimed at increasing life expectancy can aggravate the existing inequality in the field of healthcare. It is important to ensure that these interventions are available to all, regardless of their socio-economic status.
6.3. Demographic consequences:
A significant increase in life expectancy can have serious demographic consequences, such as an increase in the number of elderly people and the need to adapt health and social support systems.
6.4. Philosophical questions:
An increase in life expectancy raises philosophical questions about the meaning of life, the value of aging and how we should distribute resources in a society that is becoming more and more old.
7. Future research areas
Studies of longevity genetics continue to develop. Future studies include:
7.1. Identification of new genes and genetic options:
Despite significant progress, many genes and genetic options that affect life expectancy have yet to be identified. Further GWAS, sequencing and research on model organisms are necessary to identify new genetic factors that contribute to longevity.
7.2. The study of epigenetic mechanisms:
Epigenetic changes, such as DNA methylation and histone modification, can affect genes and play a role in aging and longevity. The study of the epigenetic mechanisms of longevity is a promising field of research.
7.3. Development of interventions aimed at longevity genes:
The identification of genes and genetic options associated with longevity can lead to the development of new interventions aimed at these genes in order to increase life expectancy and improve health in old age.
7.4. Omski data integration:
The integration of these genomics, transcription, proteomics and metabolomics can provide a more complete idea of the biological processes involved in aging and longevity.
7.5. Development of personalized medicine:
Understanding the genetic basis of longevity can lead to the development of personalized medicine strategies that are adapted to the human genetic profile, in order to optimize health and increase life expectancy.
8. Clinical applications of longevity genetics
Although the genetics of longevity is still in the early stages of development, it has the potential for clinical use in the future.
8.1. Assessment of the risk of developing age diseases:
Genetic testing can be used to assess the risk of developing age diseases, such as Alzheimer’s disease, cardiovascular diseases and cancer. This can allow people to take preventive measures to reduce their risk.
8.2. Development of new drugs and therapy:
The identification of genes involved in aging and longevity can lead to the development of new drugs and therapy, which are aimed at these genes, in order to slow down the aging process and prevent age -related diseases.
8.3. Development of healthy aging strategies:
Understanding the genetic factors that affect life expectancy can lead to the development of healthy aging strategies that are adapted to the human genetic profile. These strategies may include recommendations on the diet, physical exercises and other lifestyle factors.
8.4. Optimization of treatment:
Genetic information can be used to optimize the treatment of age -related diseases, for example, by choosing drugs that are more likely to be effective for people with a certain genetic profile.
9. Advantages and restrictions of studies of longevity genetics
9.1. Advantages:
- A deeper understanding of aging: Studies of longevity genetics provide valuable information about biological processes underlying aging, which can lead to the development of new strategies for the prevention and treatment of age -related diseases.
- Development of new drugs and therapy: The identification of genes involved in aging and longevity can lead to the development of new drugs and therapy, which are aimed at these genes, in order to slow down the aging process and prevent age -related diseases.
- Development of healthy aging strategies: Understanding the genetic factors that affect life expectancy can lead to the development of healthy aging strategies that are adapted to the human genetic profile.
- Assessment of the risk of developing age diseases: Genetic testing can be used to assess the risk of developing age diseases, which can allow people to take preventive measures to reduce their risk.
9.2. Restrictions:
- Complexity: Longevity is a complex sign, which is affected by many genes and environmental factors, which makes it difficult to identify specific genes that play a role.
- Genetic heterogeneity: Genetic factors contributing to longevity can vary between different people and populations, which complicates the generalization of research results.
- Interaction Gen-Occupation: Genetic factors can interact with environmental factors, which makes it difficult to highlight the influence of genes on life expectancy.
- Ethical problems: Studies of longevity genetics raise important ethical issues that must be taken into account.
- Limited prognostic value: Genetic tests for longevity have limited prognostic value, since they do not take into account all the factors that affect life expectancy.
10. The role of the lifestyle in longevity against the background of a genetic predisposition
Despite the significance of genetics, lifestyle plays a decisive role in realizing the potential of longevity. Even with a favorable genetic profile, an unhealthy lifestyle can significantly reduce life expectancy. Conversely, a healthy lifestyle can compensate for an adverse genetic predisposition and help increase life expectancy.
10.1. Diet:
A healthy diet, rich in fruits, vegetables, whole cereals and low -fat proteins, is important for longevity. The limitation of calorie content and interval starvation were also associated with an increase in life expectancy in some model organisms.
10.2. Exercise:
Regular physical exercises have numerous health benefits, including reducing the risk of cardiovascular diseases, diabetes, cancer and other age diseases. They can also improve cognitive functions and mental health.
10.3. Refusal of smoking and moderate alcohol use:
Smoking is the main cause of death that can be avoided. Refusal of smoking can significantly increase life expectancy. The moderate use of alcohol (no more than one drink per day for women and two drinks per day for men) may be associated with some health benefits, but excessive alcohol use is harmful to health.
10.4. Stress management:
Chronic stress can negatively affect health and reduce life expectancy. Stress management methods, such as meditation, yoga and tai-chi, can help reduce stress levels and improve the overall health.
10.5. Dream:
A sufficient dream is important for health and longevity. Most adults take from 7 to 8 hours of sleep per day.
10.6. Social activity:
Maintaining strong social ties is associated with improving health and longevity.
Thus, genetics provides only a starting point. A healthy lifestyle is the key to revealing the genetic potential of longevity and ensuring healthy and active aging.
11. Final remarks
The study of longevity genetics is a complex, but promising area. Although there is still a lot to learn about genetic factors that affect life expectancy, the progress achieved has already allowed to obtain valuable information about biological processes involved in aging and longevity. In the future, studies of longevity genetics can lead to the development of new strategies for the prevention and treatment of age -related diseases, as well as to increase life expectancy and improve health in old age. It is important to remember that genetics is not the only determining power of longevity, and a healthy lifestyle plays a decisive role in realizing the potential of longevity. Continuing research, combined with ethical considerations and responsible clinical applications, can pave the way to a healthier and more long life for everyone.