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
Journal ArticleDOI
Socioeconomic inequalities in death from past to present: A postscript☆
Journal ArticleDOI
Copy Number Variations in Alternative Splicing Gene Networks Impact Lifespan
Joseph T. Glessner,Albert V. Smith,Saarene Panossian,Cecilia E. Kim,Nagahide Takahashi,Kelly A. Thomas,Fengxiang Wang,Kallyn Seidler,Tamara B. Harris,Lenore J. Launer,Brendan J. Keating,John J. Connolly,Patrick M. A. Sleiman,Joseph D. Buxbaum,Struan F.A. Grant,Struan F.A. Grant,Vilmundur Gudnason,Hakon Hakonarson,Hakon Hakonarson +18 more
TL;DR: It is concluded that genetic variations disrupting RNA splicing could have long-term biological effects impacting lifespan.
Journal ArticleDOI
A scan for genes associated with cancer mortality and longevity in pedigree dog breeds
Aoife Doherty,Inês Lopes,Christopher T. Ford,Gianni Monaco,Patrick Guest,João Pedro de Magalhães +5 more
TL;DR: It is validated previous findings that breeds with higher average body weight have higher cancer mortality rates and lower life expectancy and identified a significant positive correlation between life span and cancer mortality residuals corrected for body weight.
Journal ArticleDOI
Association between Dopamine Receptor D2 (DRD2) Variations rs6277 and rs1800497 and Cognitive Performance According to Risk Type for Psychosis: A Nested Case Control Study in a Finnish Population Sample
Hugh Ramsay,Jennifer H. Barnett,Jouko Miettunen,Sari Mukkala,Pirjo Mäki,Johanna Liuhanen,Graham K. Murray,Marjo-Riitta Järvelin,Hanna Ollila,Tiina Paunio,Juha Veijola +10 more
TL;DR: The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ accordingto the type (familial or clinical) risk for psychosis.
Journal ArticleDOI
Investigation of complement component C4 copy number variation in human longevity.
Friederike Flachsbart,Amke Caliebe,Femke-Anouska Heinsen,Tom Hemming-Karlsen,Stefan Schreiber,Andre Franke,Almut Nebel +6 more
TL;DR: The role of the C4 alleles was investigated in a large German longevity sample (∼700 cases; 94–110 years and ∼900 younger controls) and no significant differences in the number of C4A, C4B and C4S were detected.
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.