Introduction
Advancements in medical science and nutritional awareness have increased the average human lifespan globally. The aging process is influenced by various factors, including genetics. While many factors contribute to the aging process, about 40% of human life expectancy is inherited through generations. Therefore, numerous genes, genetic mechanisms, and pathways are known to play a role in the regulation of lifespan. This article aims to evaluate over fifty genes, including their non-human orthologs, reported in the literature for their contributions to longevity.
DNA Damage Repair Mechanisms:
DNA repair mechanisms are essential for the maintenance of genomic integrity. Efficient DNA repair mechanisms can prevent the accumulation of DNA damage, leading to signaling cascades that may result in cell cycle arrest or apoptosis. DNA modifications, such as DNA methylation, histone methylation, histone acetylation, and DNA damage, can eventually lead to apoptosis. Therefore, DNA damage repair mechanisms play a vital role in regulating lifespan.
Studies have shown that genetic defects in DNA damage repair mechanisms can result in accelerated aging and increased susceptibility to cancer. Some genes involved in DNA damage repair mechanisms that have been implicated in regulating lifespan include BRCA1, BRCA2, and p53.
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Genes Associated with Longevity:
Researchers have identified several genes that are linked to longevity. For example, multiple genome-wide association studies (GWAS) have reported on the gene encoding apolipoprotein (APOE). APOE is responsible for lipid transport and metabolism and is associated with Alzheimer’s disease. The APOE ε4 allele is linked to a higher risk of Alzheimer’s disease and a shorter lifespan, whereas the APOE ε2 allele is linked to a lower risk of Alzheimer’s disease and a longer lifespan.
Another gene associated with longevity is the FOXO3A gene, which is involved in regulating stress resistance and metabolism. Studies have shown that individuals with specific variants of the FOXO3A gene have a higher chance of living to 100 years or more.
Antioxidant and Anti-Aging Properties:
Studies have suggested that the application of antioxidants can promote the expression of age-related genes, resulting in an increased lifespan. Antioxidants can neutralize free radicals, which are reactive oxygen species that can cause oxidative damage to cells and contribute to aging and age-related diseases.
Studies have demonstrated that red wine affects the expression of genes linked to longevity, including Sirt1, catalase, p53, and manganese-superoxide dismutase. Resveratrol, a polyphenol present in red wine, has been proven to extend lifespan in different organisms, including mice and worms.
The Role of DNA Methylation and Damage in Lifespan:
Studies on bats have shown that DNA methylation is negatively linked with longevity, while DNA damage is positively linked. Additionally, studies on monkeys have revealed that genome flexibility and environmental adaptations also contribute to lifespan. These studies suggest that the regulation of DNA methylation and damage repair mechanisms plays a critical role in regulating lifespan.
DNA Methylation and Aging
The process of DNA methylation adds a methyl group to a cytosine residue in DNA, thereby altering gene expression. As we age, DNA methylation patterns undergo changes, resulting in some genes becoming hypermethylated, and others becoming hypomethylated. These changes can cause alterations in gene expression, which may contribute to the aging process.
Researchers have demonstrated that DNA methylation patterns relate to lifespan. An example of the link between DNA methylation patterns and lifespan was shown in a study on the Greenlandic Inuit population, where changes in DNA methylation patterns over time were associated with age-related diseases. Similarly, differences in DNA methylation patterns were associated with differences in lifespan in a study on twins. These findings suggest that DNA methylation is a crucial process in regulating lifespan and highlight the significance of genetics and longevity research.
The Role of Telomeres in Aging
Telomeres are the protective caps at the end of chromosomes, and their length decreases with age. Research has linked telomere shortening to several age-related diseases such as cardiovascular disease, Alzheimer’s disease, and cancer.
Studies have suggested that telomere length may be a predictor of lifespan. For example, a study on a population of centenarians found that they had longer telomeres than age-matched controls. Additionally, a study on rhesus monkeys found that monkeys with longer telomeres lived longer than those with shorter telomeres.
Human Populations with High Longevity
Some human populations exhibit exceptional longevity, such as the Okinawans in Japan, the Sardinians in Italy, and the Nicoyans in Costa Rica. These populations have been the subject of numerous studies, which have identified genetic and environmental factors that contribute to their longevity.
Studies have found that these populations have lower rates of age-related diseases, better immune systems, and better metabolic health than the general population. In addition, these populations have genetic variations that relate to metabolism, inflammation, and DNA repair, which studies have associated with longevity.
Conclusion
In conclusion, genetic factors play a significant role in lifespan regulation. Studies have identified numerous genes, pathways, and mechanisms that contribute to lifespan, including DNA damage repair mechanisms, calorie restriction therapy, and telomeres. Understanding these factors can help us develop strategies to promote healthy aging and reduce the risk of age-related diseases. Additionally, studies of human populations with exceptional longevity can provide insight into the genetic and environmental factors that contribute to healthy aging. Ultimately, improving our understanding of the factors that contribute to lifespan can help us lead longer, healthier lives.
Read More: Genes and Longevity of Lifespan