Longer Lived Parents: Protective Associations With Cancer Incidence and Overall Mortality

Dutta, Ambarish; Henley, William; Robine, Jean-Marie; Langa, Kenneth M.; Wallace, Robert B.; Melzer, David

doi:10.1093/gerona/glt061

Cited by 45 publications

(81 citation statements)

References 29 publications

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“…(2013a) in the human InCHIANTI population study as well as in mice (Table 1). HNRNPA2B1 transcripts demonstrated increased expression in the offspring of long‐lived parents (beta coefficients 0.12, P = 0.017), whereas HNRNPA1 demonstrated reduced expression in the offspring of long‐lived parents (beta coefficient −0.09; P = 0.035, respectively; Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Previous work from our group has identified that offspring of long‐lived parents may have better health (Dutta et al ., 2013a,b). In the current study, two of the associations between splicing factor expression and longevity were also seen in RNA samples derived from the peripheral blood of participants in the InCHIANTI study (Ferrucci et al ., 2000), where we found relationships between expression of the HNRNPA2B1 and HNRNPA1 transcripts and parental longevity.…”

Section: Discussionmentioning

confidence: 99%

“…Short‐, intermediate‐ and long‐lived cut‐offs were calculated separately for mothers and fathers based on the normal distribution of age at death in the cohort, as described in Dutta et al . (2013a). The cut‐offs for mothers were as follows: short‐lived (49–72 years), intermediate‐lived (72–95 years) and long‐lived (> 95 years); mothers aged < 49 years at death were classed as premature and excluded.…”

Section: Methodsmentioning

confidence: 99%

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Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans

Lee¹,

Pilling

Emond³

et al. 2016

Aging Cell

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SummaryDysregulation of splicing factor expression and altered alternative splicing are associated with aging in humans and other species, and also with replicative senescence in cultured cells. Here, we assess whether expression changes of key splicing regulator genes and consequent effects on alternative splicing are also associated with strain longevity in old and young mice, across 6 different mouse strains with varying lifespan (A/J, NOD.B10Sn‐H2b/J, PWD.Phj, 129S1/SvlmJ, C57BL/6J and WSB/EiJ). Splicing factor expression and changes to alternative splicing were associated with strain lifespan in spleen and to a lesser extent in muscle. These changes mainly involved hnRNP splicing inhibitor transcripts with most changes more marked in spleens of young animals from long‐lived strains. Changes in spleen isoform expression were suggestive of reduced cellular senescence and retained cellular proliferative capacity in long‐lived strains. Changes in muscle isoform expression were consistent with reduced pro‐inflammatory signalling in longer‐lived strains. Two splicing regulators, HNRNPA1 and HNRNPA2B1, were also associated with parental longevity in humans, in the InCHIANTI aging study. Splicing factors may represent a driver, mediator or early marker of lifespan in mouse, as expression differences were present in the young animals of long‐lived strains. Changes to alternative splicing patterns of key senescence genes in spleen and key remodelling genes in muscle suggest that correct regulation of alternative splicing may enhance lifespan in mice. Expression of some splicing factors in humans was also associated with parental longevity, suggesting that splicing regulation may also influence lifespan in humans.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans

Lee¹,

Pilling

Emond³

et al. 2016

Aging Cell

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“…The above-mentioned literature provides mixed evidence for a lower cancer occurrence as a mechanism for clustering of longevity in families. While some animal studies indicate a trade-off mechanism between aging and the risk of cancer [20–24], two more recent studies suggest that familial longevity enrichment is associated with lower cancer incidence [25, 26]. In the following, we take advantage of Danish population registers, and the screening of long-lived families in three nationwide studies to shed light on possible mechanisms by comparing incidence of all cancers except non-melanoma skin cancer, as well as incidence of specific common cancer types: breast cancer, colon cancer, prostate cancer, lung cancer, and tobacco-related cancer in the long-lived families, with population-based cancer incidence rates stratified for gender, age and calendar period.…”

Section: Introductionmentioning

confidence: 99%

Low tobacco-related cancer incidence in offspring of long-lived siblings: a comparison with Danish national cancer registry data

Pedersen

Skytthe

Honig

et al. 2015

Annals of Epidemiology

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Purpose Familial clustering of longevity is well documented and includes both genetic and other familial factors, but the specific underlying mechanisms are largely unknown. We examined whether low incidence of specific cancers is a mechanism for familial clustering of longevity. Methods The study-population of individuals from longevity-enriched families consisted of 3267 offspring from 610 Danish long-lived families defined by two siblings attaining an age of 90+. The offspring of the long-lived siblings were followed 1968–2009. Using high quality registry data, observed numbers of cancers were compared to expected numbers based on gender-, calendar period-, and age-specific incidence rates in the general population. Results During the 41 year follow-up period, a total of 423 cancers occurred in 397 individuals. The standardized incidence ratios (SIRs) (95% confidence interval) for offspring of long-lived individuals were 0.78 (0. 70, 0.86) for overall cancer; 0.66 (0.56, 0.77) for tobacco-related cancer; 0.34 (0.22, 0.51) for lung cancer; 0.88 (0.71, 1.10) for breast cancer; 0.91 (0.62, 1.34) for colon cancer. Conclusions The low incidence of tobacco-related cancers in long-lived families compared to non-tobacco-related cancers suggests that health behavior plays a central role in lower early cancer incidence in offspring of long-lived siblings in Denmark.

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“…Furthermore, centenarians often display unique, healthy metabolic signatures compared to the average elderly individual of between 70 and 90 years old [4,5]. The strong genetic component of extreme longevity is underscored by the observation that offspring of centenarians inherit some of the metabolic signatures and disease profiles from their successful parent(s) [6•], including favorable lipid profiles [7], delayed onset of cognitive impairment [8,9] and reduced cancer incidence [10]. …”

Section: Introductionmentioning

confidence: 99%

Genome maintenance and human longevity

Cho

Suh

2014

Current Opinion in Genetics & Development

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Accumulation of DNA damage and mutations is considered an important causal factor in age-related diseases. Genetic defects in DNA repair cause premature onset and accelerated progression of aging-related diseases and a shorter life span in humans and mice, providing strong evidence that genome maintenance is a bona fide longevity assurance pathway. However, the contribution of genome maintenance to human longevity itself remains to be established. Here, we review the results of human genetics studies, including genome wide association studies, and attempted to catalogue all genes involved in major DNA repair pathways that harbor variants associated with longevity. We hope to provide a comprehensive review to facilitate future endeavors aimed at uncovering the functional role of genome maintenance genes in human longevity.

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Longer Lived Parents: Protective Associations With Cancer Incidence and Overall Mortality

Abstract: The results provide the first robust evidence that increasing parental attained age is associated with lower cancer incidence in offspring. Health advantages of having centenarian parents extend to a wider range of parental longevity and may provide a quantitative trait of slower aging.

Cited by 45 publications

References 29 publications

Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans

Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans

Low tobacco-related cancer incidence in offspring of long-lived siblings: a comparison with Danish national cancer registry data

Genome maintenance and human longevity

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