What are the factors that influence human development and lifespan?
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Factors Influencing Human Development and Lifespan
Genetic Factors in Lifespan Regulation
Genetic factors play a significant role in determining human lifespan, accounting for approximately 20-40% of the variation in life expectancy2 4 7. Studies have identified several genes and genetic pathways that influence longevity, including the DAF-16/FOXO, TOR, and JNK pathways2. These genes are involved in crucial cellular processes such as DNA repair, stress resistance, and metabolic regulation2 6. For instance, the FOXO family of transcription factors is conserved across species and regulates longevity by influencing stress resistance and metabolism10. Additionally, genome-wide association studies have identified specific genetic loci, such as HLA-DQA1/DRB1 and LPA, that are associated with increased lifespan3.
Environmental and Lifestyle Factors
Environmental and lifestyle factors significantly impact human development and lifespan. Early life exposures, such as maternal age, smoking, socioeconomic status, and nutritional status, can have profound implications for an individual's ageing trajectory1. These factors can affect fetal growth and placental development, leading to long-term health consequences1. Moreover, lifestyle choices such as smoking cessation, educational attainment, and maintaining a healthy body mass index (BMI) are positively correlated with increased lifespan3. Conversely, factors like obesity, insulin resistance, and high body fat negatively impact longevity3.
Nutrition and Longevity
Nutrition is a critical component influencing lifespan. Caloric restriction without malnutrition, methionine restriction, and lower protein intake have been associated with increased lifespan in model organisms5. In humans, diets rich in whole grains, vegetables, fruits, nuts, and coffee are linked to reduced all-cause mortality, while high intake of red and processed meats is associated with higher mortality rates5. The Mediterranean diet, known for its high-quality nutritional profile, is also associated with reduced mortality risk5.
Molecular and Cellular Mechanisms
The ageing process is driven by the accumulation of molecular damage, which affects cell and tissue function1. Efficient DNA repair mechanisms are essential for maintaining genomic integrity, as damaged DNA can lead to cell cycle arrest or apoptosis2. Evolutionarily conserved mechanisms, such as the insulin/insulin-like growth factor and Target of Rapamycin (TOR) signaling pathways, play a role in regulating ageing and are linked to extended healthy lifespan in various organisms9. Additionally, autophagy and mitochondrial activity are crucial in protecting against ageing-related damage9.
Epigenetic Influences
Early life exposures can lead to aberrant patterns of epigenetic marks that persist throughout life, affecting cell defense mechanisms and contributing to ageing1. These epigenetic changes can result in long-term alterations in gene expression, influencing an individual's susceptibility to age-related diseases and overall lifespan1.
Conclusion
Human development and lifespan are influenced by a complex interplay of genetic, environmental, and lifestyle factors. Genetic predispositions, early life exposures, nutritional choices, and molecular mechanisms all contribute to the ageing process and longevity. Understanding these factors can help in developing strategies to promote healthy ageing and extend lifespan.
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Most relevant research papers on this topic
Early determinants of the ageing trajectory.
Early life exposures, such as maternal factors, can significantly impact an individual's ageing trajectory and the development of age-related diseases.
Genes and Longevity of Lifespan
This review highlights the importance of genes and cellular pathways in extending lifespan, with calorie restriction therapy playing a key role in extending lifespan.
Literature ReviewGenome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity
HLA-DQA1/DRB1 and LPA genes, educational attainment, and HDL cholesterol levels positively influence human longevity, while smoking, obesity, and high BMI negatively impact it.
Meta-Analysis
Highly CitedGenetic influence on human lifespan and longevity
Genetic influence on human lifespan increases after age 60, with male monozygotic twins having a greater chance of reaching old age than female dizygotic twins.
Observational Study
Very Rigorous JournalHighly CitedNutrition and longevity – From mechanisms to uncertainties
Caloric restriction, methionine restriction, lower protein intake, and spermidine supplementation are key factors in extending lifespan in model organisms and rodents, while high intake of whole grains, vegetables, fruits, nuts, and coffee reduces all-cause mortality risk.
Literature ReviewLifespan Regulation by Evolutionarily Conserved Genes Essential for Viability
64 essential genes essential for Caenorhabditis elegans development extend lifespan when inactivated postdevelopmentally, suggesting that insulin-signaling pathways play a role in aging regulation at any stage of life.
Highly CitedThe genetics of human longevity: an intricacy of genes, environment, culture and microbiome
Life-long genetic and environmental factors, including the microbiome, play a complex role in human longevity, with environmental factors, lifestyle changes, and social and cultural influences also contributing.
Literature ReviewHighly CitedThe genetics of human ageing
Genetics can help understand the underlying mechanisms of human ageing, potentially leading to the discovery of anti-ageing interventions.
Highly CitedAgeing as a Risk Factor for Disease
Ageing is influenced by evolutionary conserved mechanisms, and understanding these relationships can help prevent diseases like cancer, cardiovascular disease, and neurodegeneration.
Highly CitedLong live FOXO: unraveling the role of FOXO proteins in aging and longevity
FOXO proteins play a crucial role in aging and longevity, contributing to healthy aging and extreme longevity in various animal models and humans.
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