Human lifespan and sex-specific patterns of resilience to disease: a retrospective population-wide cohort study

Abstract

Background: Slower paces of aging are related to lower risk of developing diseases and premature death. Therefore, the greatest challenge of modern societies is to ensure that the increase in lifespan is accompanied by an increase in health span. To better understand the differences in human lifespan, new insight concerning the relationship between lifespan and the age of onset of diseases, and the ability to avoid them is needed. We aimed to comprehensively study, at a population-wide level, the sex-specific disease patterns associated with human lifespan.

Methods: Observational data from the SIDIAP database of a cohort of 482,058 individuals that died in Catalonia (Spain) at ages over 50 years old between the 1st of January 2006 and the 30th of June 2022 were included. The time to the onset of the first disease in multiple organ systems, the prevalence of escapers, the percentage of life free of disease, and their relationship with lifespan were evaluated considering sex-specific traits.

Results: In the study cohort, 50.4% of the participants were women and the mean lifespan was 83 years. The results show novel relationships between the age of onset of disease, health span, and lifespan. The key findings include: Firstly, the onset of both single and multisystem diseases is progressively delayed as lifespan increases. Secondly, the prevalence of escapers is lower in lifespans around life expectancy. Thirdly, the number of disease-free systems decreases until individuals reach lifespans around 87-88 years old, at which point it starts to increase. Furthermore, long-lived women are less susceptible to multisystem diseases. The associations between health span and lifespan are system-dependent, and disease onset and the percentage of life spent free of disease at the time of death contribute to explaining lifespan variability. Lastly, the study highlights significant system-specific disparities between women and men.

Conclusions: Health interventions focused on delaying aging and age-related diseases should be the most effective in increasing not only lifespan but also health span. The findings of this research highlight the relevance of Electronic Health Records in studying the aging process and open up new possibilities in age-related disease prevention that should assist primary care professionals in devising individualized care and treatment plans.

Keywords: Age-related diseases; Aging; Electronic health records; Escapers; Health span; Human lifespan; Primary care.

Fig. 1

Kaplan-Meier curves for the onset of age-related diseases in different biological systems according to age of death, stratified by sex. The proportion of individuals free of disease (y-axis) at each age (x-axis) is represented stratifying by lifespan of individuals and sex. Each panel includes the curves from both sexes corresponding to the same system. Curves that decay earlier indicate a higher risk of an early onset of the disease. Age of onset is considered as the age of diagnosis of the first disease in the system. The specific diseases belonging to each category can be found in Additional file 2

Fig. 2

Evolution of the prevalence of escapers (individuals that died without a specific disease) according to the lifespan of the individuals. A higher prevalence of escapers indicates lower chance of developing the disease. A Overview of all the systems for both sexes. Dashed lines correspond to women, and solid lines correspond to men. B Systems grouped into similar evolution clusters using k-means clustering specific to each sex. The specific diseases belonging to each category can be found in Additional file 2

Fig. 3

Evolution of multisystem involvement according to the lifespan of the individuals. A Cumulative prevalence of individuals with decreasing number of systems free of disease at death (from 8 to 0) according to the lifespan of the individuals, specifically for women and men. A higher cumulative prevalence indicates a globally higher number of systems free of disease at death. C Comparison by sex of the prevalence of individuals with each number of systems free of disease according to their lifespan. Dashed lines correspond to women, and solid lines correspond to men. D Evolution of the number of systems free of disease for both sexes. Dashed lines correspond to women, and solid lines correspond to men

Fig. 4

Evolution of the percentage of life free of disease according to the lifespan of the individuals. Higher percentages of life free of disease indicate longer health spans. A Overview of all the systems for both sexes. Dashed lines correspond to women, and solid lines correspond to men. B Systems grouped into similar evolution clusters using k-means clustering specific to each sex. The specific diseases belonging to each category can be found in Additional file 2

Fig. 5

Multiple factor analysis on sex, number of systems free of disease, involvement in a system, and the percentage of life free of disease in the different systems. A Score plots from a random subset of 4821 individuals colored according to their lifespan. Closer points correspond to more similar individuals. B contribution of the groups of variables to the first two dimensions. Dashed red line: expected value considering uniform contributions

Fig. 6

Summary of the main results of the study. Images partially created with BioRender.com