The genetics of exceptional longevity: Insights from centenarians

Santos‐Lozano, Alejandro; Santamarina, Ana; Pareja‐Galeano, Helios; Sanchís-Gomar, Fabián; Fiuza‐Luces, Carmen; Cristi-Montero, Carlos; Bernal-Pino, Aranzazu; Lucía, Alejandro; Garatachea, Nuria

doi:10.1016/j.maturitas.2016.05.006

Cited by 33 publications

(33 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Four of these SNPs were located in or nearby genes that are also associated with DNA repair and maintenance (APOE, FOXO, interleukins, and tumor necrosis factor-α). 47 A large population-based Dutch study among 4,000 postmenopausal women revealed that late first and last reproductive events were protective for all-cause mortality. 48 Indeed, there seem to be a reciprocal relationship between fertility and mortality.…”

Section: Longevity and Menopausementioning

confidence: 99%

Genetics of Menopause and Primary Ovarian Insufficiency: Time for a Paradigm Shift?

Laven

2020

Semin Reprod Med

View full text Add to dashboard Cite

This review summarizes the existing information concerning the genetic background of menopause and primary ovarian insufficiency (POI). There is overwhelming evidence that majority of genes are involved in double-strand break repair, mismatch repair, and base excision repair. The remaining loci were involved in cell energy metabolism and immune response. Gradual (or in case of rapid POI) accumulation of unrepaired DNA damage causes (premature) cell death and cellular senescence. This in turn leads to exhaustion of cell renewal capacity and cellular dysfunction in affected organs and eventually to aging of the entire soma. Similar erosion of the genome occurs within the germ cell line and the ovaries. Subsequently, the systemic “survival” response intentionally suppresses the sex-steroid hormonal output, which in turn may contribute to the onset of menopause. The latter occurs in particular when age-dependent DNA damage accumulation does not cease. Both effects are expected to synergize to promote (premature) ovarian silencing and install (early) menopause. Consequently, aging of the soma seems to be a primary driver for the loss of ovarian function in women. This challenges the current dogma which implies that loss of ovarian function initiates aging of the soma. It is time for a paradigm shift!

show abstract

Section: Longevity and Menopausementioning

confidence: 99%

Genetics of Menopause and Primary Ovarian Insufficiency: Time for a Paradigm Shift?

Laven

2020

Semin Reprod Med

View full text Add to dashboard Cite

show abstract

“…While interest in genetic determinants of longevity in humans has grown significantly as gene mapping methods have become more powerful, there are still comparatively few robustly mapped, replicated natural variants that modulate longevity. Only the TOMM40/APOE/APOC1 gene cluster (19q13.11–19q13.32) and the FOXO3 gene (6q21) can make this claim [46, 91, 153–154]. Apolipoprotein E ( APOE ) has two isoforms known to influence longevity through their association with disease, APOE ε2 and APOE ε4 [48] .…”

Section: Mapping Longevity Gene Variants In Humansmentioning

confidence: 99%

Genetic cartography of longevity in humans and mice: Current landscape and horizons

Hook

Roy

Williams

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

Aging is a complex and highly variable process. Heritability of longevity among humans and other species is low, and this finding has given rise to the idea that it may be futile to search for DNA variants that modulate aging. We argue that the problem in mapping longevity genes is mainly one of low power and the genetic and environmental complexity of aging. In this review we highlight progress made in mapping genes and molecular networks associated with longevity, paying special attention to work in mice and humans. We summarize 40 years of linkage studies using murine cohorts and 15 years of studies in human populations that have exploited candidate gene and genome-wide association methods. A small but growing number of gene variants contribute to known longevity mechanisms, but a much larger set have unknown functions. We outline these and other challenges and suggest some possible solutions, including more intense collaboration between research communities that use model organisms and human cohorts. Once hundreds of gene variants have been linked to differences in longevity in mammals, it will become feasible to systematically explore gene-by-environmental interactions, dissect mechanisms with more assurance, and evaluate the roles of epistasis and epigenetics in aging. A deeper understanding of complex networks-genetic, cellular, physiological, and social-should position us well to improve healthspan.

show abstract

“…Además, este estudio se replicó y se encontró un efecto significativo del gen combinado GHSRMREA11, el cual tiene una gran influencia en la supervivencia longitudinal en mujeres nonagenarias (Dato, y otros, 2018). Por último, según los datos obtenidos por Santos et al (2016), hay SNPs para la longevidad humana (rs429358, rs2802292, rs13217795, rs2764264, rs1042522, rs7762395, rs1800896), otros perjudiciales, o con ningún impacto.…”

Section: Biológicosunclassified

Desarrollo evolutivo humano y longevidad. Un análisis bio-psicosocial

García

Macías

Suárez

et al. 2020

RIP

View full text Add to dashboard Cite

En este trabajo se hace una revisión bibliográfica sobre el desarrollo evolutivo humano y longevidad, desde un enfoque biopsicosocial (Engel, 1977; Gliedt et al., 2017; Lehman et al., 2017). Tras aplicar el método de análisis PRISMA, se obtuvieron diversos resultados relacionados con un desarrollo evolutivo más longevo; así, en el área biológica, 3 factores: los SNPs, los telómeros y la química del estrés; en el área psicológica, 5 factores: la metacognición, la resiliencia, la espiritualidad, las relaciones personales y la depresión; y en el área social, 8 factores: la pseudo-heredabilidad, las relaciones conyugales, la maternidad, el nivel educativo, estilos de vida, dieta y restricción calórica, actividad física y mental y tecnología sanitaria. Ante los datos obtenidos en las tres áreas, de este enfoque biopsicosocial, y el repetido solapamiento entre factores del área psicológica y del área social, se plantea que pudieran considerarse estas dos como una conjunta, proponiéndose un enfoque explicativo con dos áreas: bio-psicosocial que, por factores encontrados en este trabajo, quedarían un 18,7% de biológica y un 81,3% psicosocial. Actualmente, hay suficiente información sobre desarrollo evolutivo humano y longevidad, pero una ausencia de investigaciones que estudien esos factores desde una perspectiva integrada. Mucha de esa información privilegiada se podría aplicar ya, psicológica y socialmente, a la población en general, para una mejora de su salud, en cualquier fase del desarrollo evolutivo humano.

show abstract

The genetics of exceptional longevity: Insights from centenarians

Cited by 33 publications

References 95 publications

Genetics of Menopause and Primary Ovarian Insufficiency: Time for a Paradigm Shift?

Genetics of Menopause and Primary Ovarian Insufficiency: Time for a Paradigm Shift?

Genetic cartography of longevity in humans and mice: Current landscape and horizons

Desarrollo evolutivo humano y longevidad. Un análisis bio-psicosocial

Contact Info

Product

Resources

About