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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Parental longevity correlates with offspring's optimism in two cohorts of community-dwelling older subjects.
Nathaly Rius-Ottenheim,Daan Kromhout,Anton J. M. de Craen,Johanna M. Geleijnse,Roos C. van der Mast,Frans G. Zitman,Rudi G. J. Westendorp,P. Eline Slagboom,Erik J. Giltay +8 more
TL;DR: In conclusion, parental longevity was positively associated with optimism in adult offspring, suggesting a partial linked heritability of longevity and optimism.
Journal ArticleDOI
A TOMM40/APOE allele encoding APOE-E3 predicts high likelihood of late-onset Alzheimer's disease in autopsy cases.
Selma M. Soyal,Markus Kwik,Ognian Kalev,Stefan Lenz,Greta Zara,Peter Strasser,Wolfgang Patsch,Serge Weis +7 more
TL;DR: The striking association of TOMM 40 only with high likelihood AD may explain some contrasting results for TOMM40 in clinical studies and may reflect an association with more advanced disease and/or suggest a role of TOMm40 in the pathogenesis of neurofibrillary tangles.
Journal ArticleDOI
AKT1 fails to replicate as a longevity-associated gene in Danish and German nonagenarians and centenarians.
Marianne Nygaard,Marianne Nygaard,Mette Soerensen,Mette Soerensen,Friederike Flachsbart,Jonas Mengel-From,Jonas Mengel-From,Qihua Tan,Qihua Tan,Stefan Schreiber,Almut Nebel,Kaare Christensen,Kaare Christensen,Lene Christiansen,Lene Christiansen +14 more
TL;DR: The results do not support AKT1 as a universal longevity-associated gene, although a supportive nominal indication of a disadvantageous effect of rs3803304 was found in a restricted group of Danish centenarian men.
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References
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