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ABSTRACT: Background
Previous researched has demonstrated potent health and survival advantages across three-generations in longevity-enriched families. However, the survival advantage associated with familial longevity may manifest earlier in life than previously thought.Methods
We conducted a matched cohort study comparing early health trajectories in third-generation grandchildren (n = 5,637) and fourth-generation great-grandchildren (n = 14,908) of longevity-enriched sibships to demographically matched births (n = 41,090) in Denmark between 1973 and 2018.Results
Lower risk was observed across a range of adverse early life outcomes in the grandchildren, including infant mortality (Hazard Ratio (HR) = 0.53, 95% CI [0.36, 0.77]), preterm birth (Odds Ratio (OR) = 0.82, [0.72, 0.93]), small for gestational age (OR = 0.83, [0.76, 0.90]) and neonatal respiratory disorders (OR = 0.77, [0.67, 0.88]). Relative advantages in parental education and maternal smoking were observed in both generations to a similar degree. However, a much smaller reduction in infant mortality was observed in the great-grandchildren (HR = 0.90, [0.70, 1.17]) and benefits across other outcomes were also less consistent, despite persisting socioeconomic and behavioural advantages. Lastly, maternal, and paternal lines of transmission were equipotent in the transmission of infant survival advantages.Conclusions
Descendants of longevity-enriched sibships exhibit a broad health advantage manifesting as early the perinatal period. However, this effect is strongly diluted over successive generations. Our findings suggest that exceptional health and survival may have early developmental components and implicate heritable genetic and or epigenetic factors in their specific transmission.
SUBMITTER: Keys MT
PROVIDER: S-EPMC11302717 | biostudies-literature | 2024 May
REPOSITORIES: biostudies-literature
Keys Matthew Thomas MT Pedersen Dorthe Almind DA Larsen Pernille Stemann PS Kulminski Alexander A Feitosa Mary F MF Wojczynski Mary M Province Michael M Christensen Kaare K
medRxiv : the preprint server for health sciences 20240506
<h4>Background</h4>Previous researched has demonstrated potent health and survival advantages across three-generations in longevity-enriched families. However, the survival advantage associated with familial longevity may manifest earlier in life than previously thought.<h4>Methods</h4>We conducted a matched cohort study comparing early health trajectories in third-generation grandchildren (n = 5,637) and fourth-generation great-grandchildren (n = 14,908) of longevity-enriched sibships to demogr ...[more]