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.read more
Citations
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A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward
TL;DR: This review ranges across a variety of APOE-related pathologies, touching on evolutionary genetics and risk mitigation by ethnicity and sex, and addresses one of the most fundamental question pertaining to APOE4 and AD: doesAPOE4 increase AD risk via a loss or gain of function?
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Human cognitive aging: Corriger la fortune?
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Association of the FOXO3A Locus with Extreme Longevity in a Southern Italian Centenarian Study
Chiara Viviani Anselmi,Alberto Malovini,Roberta Roncarati,Valeria Novelli,Francesco Villa,Gianluigi Condorelli,Riccardo Bellazzi,Annibale Alessandro Puca +7 more
TL;DR: The data point to a key role of FOXO3A in human longevity and confirm the feasibility of the identification of such genes with centenarian-controls studies and hypothesize the susceptibility to the longevity phenotype may well be the result of complex interactions involving genes and environmental factors but also gender.
References
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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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Claudio Franceschi,Massimiliano Bonafè,Silvana Valensin,Fabiola Olivieri,Maria De Luca,Enzo Ottaviani,Giovanna De Benedictis +6 more
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.
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