Familial Risk for Exceptional Longevity

Sebastiani, Paola; Andersen, Stacy L.; Nussbaum, Lisa; Stevenson, Meredith; Pierce, Leslie; Xia, Samantha; Salance, Kelly; Perls, Thomas T.

doi:10.1080/10920277.2015.1061946

Cited by 14 publications

(11 citation statements)

References 26 publications

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“…A peculiar characteristic of Sardinian familial longevity is that children born from mothers who later became centenarians had significant lower infant mortality when compared to children born to those women belonging to the same cohorts but who did not became centenarians 85 . Thus, history of familial longevity contributes to increasing the odds for an individual's longevity, as reported in a study of 1,700 sibships from families of centenarians in the New England Centenarian Study 86 . Moreover, centenarians offspring are characterized by a better health status when compared with age-matched controls born from parents who died before reaching the expected lifespan for their cohort 87 .…”

Section: Familial Ecology and The Genetic Of Longevitymentioning

confidence: 94%

Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework

Giuliani

Garagnani

Franceschi

2018

Circulation Research

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Genetics of human longevity within an eco-evolutionary nature-nurture framework. -Circulation Research 2018 ; 123(7) : 745-772.The final published version is available online at: https://www.ahajournals.org/ ABSTRACTHuman longevity is a complex trait, and to disentangle its basis has a great theoretical and practical consequence for biomedicine. The genetics of human longevity is still poorly understood, despite a number of investigations that used different strategies and protocols. Here we argue that such rather disappointing harvest is largely due to the extraordinary complexity of the longevity phenotype in humans. The capability to reach the extreme decades of human lifespan appears to be the result of an intriguing mixture of geneenvironment interactions. Accordingly, the genetics of human longevity is here described as a highly context-dependent phenomenon, within a new integrated, ecological and evolutionary perspective, and is presented as a dynamic process, both historically and individually. The available literature has been scrutinized within this perspective, paying particular attention to factors (sex, individual biography, family, population ancestry, social structure, economic status and education, among others) that have been relatively neglected. The strength and limitations of the most powerful and used tools, such as GWAS and whole-genome sequencing, have been discussed, focusing on prominently emerged genes and regions, such as APOE, FOXO3, IL-6, IGF-1, chromosome 9p21, 5q33.3 and somatic mutations among others. The major results of this approach suggest that: i) the genetics of longevity is highly population-specific; ii) small-effect alleles, pleiotropy and the "complex allele timing" likely play a major role; iii) genetic risk factors are age-specific and need to be integrated in the light of the geroscience perspective; iv) a close relationship between genetics of longevity and genetics of age-related diseases (especially cardiovascular diseases) do exist. Finally, the urgent need of a global approach to the largely unexplored interactions between the three genetics of human body, i.e. nuclear, mitochondrial and microbiomes, is stressed. We surmise that the comprehensive approach here presented will help in increasing the above-mentioned harvest.

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Section: Familial Ecology and The Genetic Of Longevitymentioning

confidence: 94%

Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework

Giuliani

Garagnani

Franceschi

2018

Circulation Research

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“…Consistent with Fries' compression of morbidity hypothesis (1), we and others have observed a progressive compression of the time that centenarians experience both disability and morbidity, particularly for survival beyond 105 years, or the oldest 0.1 percentile of survival (2)(3)(4)(5)(6). Our work on heritability of extreme longevity (EL) has also demonstrated that while the vast majority of variation in survival around average life expectancy is explained by environmental factors and health-related behaviors (7,8), genetic variants are likely to be the major predisposing factors to EL, especially beyond ages 105+ years (9,10). Therefore, studying centenarians' genomes should help discover those genetic factors that extend human lifespan and enable people to remain healthy as they age.…”

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confidence: 99%

APOEAlleles and Extreme Human Longevity

Sebastiani

Gurinovich

Nygaard

et al. 2018

The Journals of Gerontology: Series A

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118

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We assembled a collection of 28,297 participants from 7 studies of longevity and healthy aging comprising New England Centenarian, Long Life Family, Longevity Gene Population, Southern Italian Centenarian, Japanese Centenarian, the Danish Longevity and the Health and Retirement Studies to investigate the association between the APOE alleles ɛ2, ɛ3 and ɛ4 and extreme human longevity and age at death. By using 3 different genetic models and two definitions of extreme longevity based on either a threshold model or age at death, we show that ɛ4 is associated with a substantially decreased odds for extreme longevity, and increased risk for death that persists even beyond ages reached by less than 1% of the population. We also show that carrying the ɛ2ɛ3 or ɛ2ɛ3 genotype is associated with significantly increased odds to reach extreme longevity, with decreased risk for death compared to carrying the genotype ɛ2ɛ3 but with only a modest reduction in risk for death beyond an age reached by less than 1% of the population.

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“…The increasing number of analyzed genomes of the elderly, in particular, centenarians, provides insights into the genetic predisposition of exceptional longevity. [ 94–96 ] Heritability of longevity (survival beyond the oldest percentiles) increases sharply with survival beyond the age of 90, [ 97 ] suggesting the existence of specific genes variants that centenarians share. [ 98 ] However, only the APOE (apolipoprotein E protein), FOXO3 (stress‐induced transcription factor forkhead box O3), and 5q33.3 (longevity locus on chromosome 5q33.3) loci are consistently associated with longer life span across studies.…”

Section: Omics‐based Molecule‐pattern Biomarkersmentioning

confidence: 99%

Aging Biomarkers: From Functional Tests to Multi‐Omics Approaches

Kudryashova¹,

Burka²,

Kulaga

et al. 2020

Proteomics

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Aging results in various deleterious changes in the human body that may lead to loss of function and the manifestation of chronic diseases. While diseases can generally be reliably diagnosed, the aging process itself requires more sophisticated approaches to evaluate its progression. Numerous attempts have been made to establish biomarkers to quantify human aging at the cellular, tissue, and organismal level. Here, an up‐to‐date overview of biomarkers related to human aging with an emphasis on biomarkers that take into account different mechanisms of aging between individuals is provided. Classical discrete molecular and non‐molecular biomarkers handpicked by researches on the base of their strong correlation with age, as well as emerging omics‐based biomarkers, are discussed and potential future directions and developments in the field of aging assessment are outlined.

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Familial Risk for Exceptional Longevity

Cited by 14 publications

References 26 publications

Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework

Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework

APOEAlleles and Extreme Human Longevity

Aging Biomarkers: From Functional Tests to Multi‐Omics Approaches

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