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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

Genomics of human health and aging

TL;DR: The Framingham Heart Study is used to elucidate if recognizing the role of evolution and systemic processes in an aging organism could advance GWAS studies and show that both lifespan and ages at onset of CVD and cancer can be controlled by the same allelic variants.
Journal ArticleDOI

Genetic and environmental effects on mortality before age 70 years.

TL;DR: There is a genetic effect on the rate of death with infections, vascular causes, natural causes and all causes, whereas there is no indication of an influence of shared sibling environment in adoptees and their adoptive siblings.
Dissertation

Uloga polimorfizama kandidatskih gena za kardiovaskularne bolesti u dugovječnosti: antropološki pristup

TL;DR: Kardiovaskularne su bolesti (KVB) glavni uzrocnik pobola i smrtnosti diljem svijeta, a podložnost razvoju bolesta povecava interakcija okolisnih,
Journal ArticleDOI

Ovine mitochondrial DNA sequence variation and its association with production and reproduction traits within an Afec-Assaf flock.

TL;DR: The results highlight the ovine mitogenome genetic variation in protein- and tRNA coding genes and suggest that sequence variation in ovine mtDNA is associated with variation in ewe prolificacy.
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.
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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.
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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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