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The quest for genetic determinants of human longevity: challenges and insights

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TLDR
Large-scale linkage studies of long-lived families, longitudinal candidate-gene association studies and the development of analytical methods provide the potential for future progress in human studies of longevity.
Abstract
Twin studies show that genetic differences account for about a quarter of the variance in adult human lifespan. Common polymorphisms that have a modest effect on lifespan have been identified in one gene, APOE, providing hope that other genetic determinants can be uncovered. However, although variants with substantial beneficial effects have been proposed to exist and several candidates have been put forward, their effects have yet to be confirmed. Human studies of longevity face numerous theoretical and logistical challenges, as the determinants of lifespan are extraordinarily complex. However, large-scale linkage studies of long-lived families, longitudinal candidate-gene association studies and the development of analytical methods provide the potential for future progress.

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Journal ArticleDOI

Tetz’s theory and law of longevity

George Tetz, +1 more
TL;DR: It is suggested that this theory and model have explanatory and predictive potential to eukaryotic organisms, allowing the influence of diseases, medication, and medical procedures to be re-examined in relation to longevity.
BookDOI

Overview on Heterogeneity in Longevity and Pension Schemes

TL;DR: This article reviewed the empirical literature on the longevity differences across socioeconomic groups and their impacts on lifetime benefits, considering how these impacts depend on four different pay-as-you-go pension structures (calibrated on the US case).
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Longevity defined as top 10% survivors is transmitted as a quantitative genetic trait: results from large three-generation datasets

TL;DR: This work uses three-generational mortality data from two large datasets to provide strong evidence that longevity is transmitted as a quantitative genetic trait among survivors up to the top 10% of their birth cohort, and suggests to base case selection onTop 10% survivors of theirBirth cohort with equally long-lived family members.
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The relationship between reproductive and biochemical ageing at the time of the menopausal transition.

TL;DR: Gene expression profile of ageing has been studied in model systems or human blood samples, but rarely in human saliva samples, and the simplicity of saliva sample collection emphasizes the importance of saliva tissue samples in gene expression analyses especially in epidemiological surveys.
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Mortality, family and lifestyles

TL;DR: In this paper, the authors developed an overlapping generations model where a healthy lifestyle and an unhealthy lifestyle are transmitted vertically or obliquely across generations, and showed that there must exist a locally stable heterogeneous equilibrium involving a majority of healthy agents, as a result of the larger parental gains from socialization efforts under higher life expectancy.
References
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Journal ArticleDOI

Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families

TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
Journal ArticleDOI

The Future of Genetic Studies of Complex Human Diseases

TL;DR: The identification of the genetic basis of complex human diseases such as schizophrenia and diabetes has proven difficult as mentioned in this paper, and Risch and Merikangas proposed that they can best accomplish this goal by combining the power of the human genome project with association studies.
Journal ArticleDOI

Inflamm‐aging: An Evolutionary Perspective on Immunosenescence

TL;DR: The beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.
Journal ArticleDOI

The impact of heterogeneity in individual frailty on the dynamics of mortality.

TL;DR: Calculations based on Swedish mortality data suggest that standard methods overestimate current life expectancy and potential gains in life expectancy from health and safety interventions, while underestimating rates of individual aging, past progress in reducing mortality, and mortality differentials between pairs of populations.
Journal ArticleDOI

Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans

TL;DR: The findings suggest that the insulin/IGF-I pathway ultimately exerts its effect on lifespan by upregulating a wide variety of genes, including cellular stress-response, antimicrobial and metabolic genes, and by downregulating specific life-shortening genes.
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