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Open AccessJournal ArticleDOI

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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Citations
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Journal ArticleDOI

Optimal linear taxation under endogenous longevity

TL;DR: In this article, the optimal linear tax-transfer policy in an economy where agents differ in productivity and in genetic background and where longevity depends on health spending and genes was studied, and the utilitarian optimum can be decentralized with type-specific lump-sum transfers and Pigouvian taxes correcting for agents' myopia and for their misperception of health spending's effects on the economy's resources.

Centenarian research in the past two decades

TL;DR: The authors reviewed the demographic change seen in industrialised countries and the state of the literature on centenarian research, summarising findings from some of the major longitudinal studies, concluding that the focus of centenarians research has expanded and methodological approaches have become more robust.
Journal ArticleDOI

APOE haplotypes are associated with human longevity in a Central Italy population: evidence for epistasis with HP 1/2 polymorphism.

TL;DR: APOE haplotypes are significantly associated with longevity in the authors' population and of note, HP*1/*1 genotype seems to protects APOE*ε4 carriers from age-related negative selection.
Book ChapterDOI

Precedents for the Biological Control of Aging: Experimental Postponement, Prevention, and Reversal of Aging Processes

TL;DR: A body of observations implies that the future of human aging can be substantially different than its past and supports recent excitement over the possibilities of human intervention.
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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