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
Inflammaging and anti-inflammaging: A systemic perspective on aging and longevity emerged from studies in humans
Claudio Franceschi,Miriam Capri,Daniela Monti,Sergio Giunta,Fabiola Olivieri,Federica Sevini,Maria Panagiota Panourgia,Laura Invidia,Laura Celani,Maria Scurti,Elisa Cevenini,Gastone Castellani,Stefano Salvioli +12 more
TL;DR: It is proposed that inflammaging can be flanked by anti-inflammaging as major determinants not only of immunosenescence but eventually of global aging and longevity.
Journal ArticleDOI
Biodemography of human ageing.
TL;DR: Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival — and healthy survival — to even greater ages.
Journal ArticleDOI
FOXO3A genotype is strongly associated with human longevity
Bradley J. Willcox,Timothy A. Donlon,Qimei He,Randi Chen,John S. Grove,Katsuhiko Yano,Kamal Masaki,D. Craig Willcox,Beatriz L. Rodriguez,J. David Curb +9 more
TL;DR: Long-lived men presented several additional phenotypes linked to healthy aging, including lower prevalence of cancer and cardiovascular disease, better self-reported health, and high physical and cognitive function, despite significantly older ages than controls, several of these aging phenotypes were associated with FOXO3A genotype.
Journal ArticleDOI
Association of FOXO3A variation with human longevity confirmed in German centenarians
Friederike Flachsbart,Amke Caliebe,Rabea Kleindorp,Hélène Blanché,Huberta von Eller-Eberstein,Susanna Nikolaus,Stefan Schreiber,Almut Nebel +7 more
TL;DR: This study investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provided evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age, and confirmed the initial discovery in the Japanese sample.
Journal ArticleDOI
Long live FOXO: unraveling the role of FOXO proteins in aging and longevity
TL;DR: The mechanisms by which FOXO factors contribute to longevity will be discussed in diverse animal models, from Hydra to mammals, and compelling evidence of FOXOs as contributors for extreme longevity and health span in humans will be addressed.
References
More filters
Journal ArticleDOI
Apolipoprotein E Genotypes: Relationship to Cognitive Functioning, Cognitive Decline, and Survival in Nonagenarians
TL;DR: To evaluate the extent to which relationships between apolipoprotein E, cognitive functioning, and survival in people aged 60 to 80 persist into advanced old age, a large number of patients are diagnosed with dementia.
Journal ArticleDOI
Methylenetetrahydrofolate reductase polymorphism, plasma homocysteine and age.
Liliane Todesco,Christian P. Angst,P. Litynski,Franziska M. T. Loehrer,Brian Fowler,Walter E. Haefeli +5 more
TL;DR: A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR), caused by the C677T point mutation, leads to increased thermolability of the enzyme, with reduced enzyme activity.
Journal ArticleDOI
Angiotensin I-Converting Enzyme (ACE) Gene Polymorphism in Relation to Physical Performance, Cognition and Survival—A Follow-up Study of Elderly Danish Twins
Henrik Frederiksen,David Gaist,Lise Bathum,Kjeld Andersen,Matt McGue,James W. Vaupel,Kaare Christensen +6 more
TL;DR: There were no substantial effects of ACE genotype on physical and cognitive performance, or rate of change among elderly, and persons with the D allele may have a lower mortality at older ages.
Journal ArticleDOI
Do Centenarians Die Healthy? An Autopsy Study
TL;DR: Centenarians, though perceived to have been healthy just prior to death, succumbed to diseases in 100% of the cases examined, justifying autopsy as a legal requirement for this clinically difficult age group.
Journal ArticleDOI
Cholesteryl ester transfer protein (CETP) I405V polymorphism and longevity in Italian centenarians.
Elena Cellini,Benedetta Nacmias,Fabiola Olivieri,Luigi Ortenzi,Andrea Tedde,Silvia Bagnoli,Concetta Petruzzi,Claudio Franceschi,Sandro Sorbi +8 more
TL;DR: The result does not confirm the association between the I405V CETP variation and the healthy aging phenotype described in the Ashkenazi Jewish population and suggests that other gene environment interactions contribute to longevity.