The quest for genetic determinants of human longevity: challenges and insights
Reads0
Chats0
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
More filters
Posted Content
The Transmission of Longevity Across Generations
TL;DR: This paper studied the relationship between a father's age at death and his children's expected lifetime using a large and representative data set of individuals in Israel and found that after the early thirties for women and early forties for men, the survivor probability of an individual is significantly affected by the age at which her or his father died.
Journal ArticleDOI
Vieillissement et longévité : données récentes
TL;DR: Recent advances concerning the intrinsic or environmental factors that affect longevity and the physiopathology of ageing are reviewed.
Posted ContentDOI
Induction of Alzheimer's disease pathology by early-life stress
Tomoko Tanaka,Shinobu Hirai,Masato Hosokawa,Takashi Saito,Hiroshi Sakuma,Takaomi C. Saido,Masato Hasegawa,Haruo Okado +7 more
TL;DR: Findings suggest that maternal separation causes early induction of AD pathology, and hypothesize that activated microglia induced by the combination of maternal separation and APP mutation impairs the vascular system, leading to AD progression.
References
More filters
Journal ArticleDOI
Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Elizabeth H. Corder,Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,Gary W. Small,A. D. Roses,Jonathan L. Haines,Margaret A. Pericak-Vance +8 more
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
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.
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
Coleen T. Murphy,Steven A. McCarroll,Cornelia I. Bargmann,Andrew G. Fraser,Ravi S. Kamath,Julie Ahringer,Hao Li,Cynthia Kenyon +7 more
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.