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. 2025 Jan;40(1):107-122.
doi: 10.1007/s10654-024-01200-x. Epub 2025 Jan 17.

The associations of long-term physical activity in adulthood with later biological ageing and all-cause mortality - a prospective twin study

Anna Kankaanpää  1 , Asko Tolvanen  2 , Laura Joensuu  1 , Katja Waller  3 , Aino Heikkinen  4 , Jaakko Kaprio  4 , Miina Ollikainen  4   5 , Elina Sillanpää  6   7
Affiliations

The associations of long-term physical activity in adulthood with later biological ageing and all-cause mortality - a prospective twin study

Anna Kankaanpää et al. Eur J Epidemiol. 2025 Jan.

Abstract

Objectives: The association between leisure-time physical activity (LTPA) and a lower risk of mortality is susceptible to bias from multiple sources. We investigated the potential of biological ageing to mediate the association between long-term LTPA and mortality and whether the methods used to account for reverse causality affect the interpretation of this association.

Methods: Study participants were twins from the older Finnish Twin Cohort (n = 22,750; 18-50 years at baseline). LTPA was assessed using questionnaires in 1975, 1981 and 1990. The mortality follow-up lasted until 2020 and biological ageing was assessed using epigenetic clocks in a subsample (n = 1,153) with blood samples taken during the follow-up. Using latent profile analysis, we identified classes with distinct longitudinal LTPA patterns and studied differences in biological ageing between these classes. We employed survival models to examine differences in total, short-term and long-term all-cause mortality, and multilevel models for twin data to control for familial factors.

Results: We identified four classes of long-term LTPA: sedentary, moderately active, active and highly active. Although biological ageing was accelerated in sedentary and highly active classes, after adjusting for other lifestyle-related factors, the associations mainly attenuated. Physically active classes had a maximum 7% lower risk of total mortality over the sedentary class, but this association was consistent only in the short term. After accounting for familial factors and excluding participants reporting prevalent cardiovascular diseases, LTPA exhibited less favourable associations with mortality.

Conclusion: The association between LTPA and lower all-cause mortality may be largely due to genetic confounding and reverse causality.

Keywords: Biological age; DNA methylation; Lifespan; Mortality; Physical activity.

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Conflict of interest statement

Declarations. Ethical approval: Data collection was conducted in accordance with the Declaration of Helsinki. The ethics committees of the University of Helsinki and Helsinki University Central Hospital approved the study protocol (113/E3/2001 and 346/E0/05). Consent to participate: Blood samples for DNA analyses were collected during in-person clinical studies after written informed consent was signed. Data sharing: A subsample of the FTC with DNA methylation age estimates, phenotypes and information on the classes of long-term LTPA will be located in the Biobank of the National Institute for Health and Welfare. All these data will be publicly available for use by qualified researchers following a standardised application procedure (for details on the application process, see the following website: https://thl.fi/en/web/thl-biobank/for-researchers ). Because of the consent given by the study participants and the high degree of identifiability of the twin siblings in Finland, the full cohort data cannot be made publicly available. However, the full cohort data are available through the Institute for Molecular Medicine Finland (FIMM) Data Access Committee (DAC) for authorised researchers with an IRB/ethics approval and an institutionally approved study plan. For more details, please contact the FIMM DAC (fimm-dac@ helsinki.fi). Competing interests: The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Path diagram of the discrete-time survival models for (A) total mortality and (B) short- and long-term mortality. Follow-up time was treated as time scale in the analysis. Circles denote latent variables and rectangles observed variables LTPA, leisure-time physical activity; u, discrete-time survival indicators
Fig. 2
Fig. 2
Patterns of long-term leisure-time physical activity (n = 22,750)
Fig. 3
Fig. 3
Mean differences between the long-term leisure-time physical activity classes in terms of biological ageing measured using (A)–(C) PC-based GrimAge and (D)–(F) DunedinPACE (n = 1,153)
Fig. 4
Fig. 4
Associations of long-term leisure-time physical activity with (A) total mortality, (B) short-term mortality (1990–2011) and (C) long-term mortality (2012–2020) (n = 22,750)
Fig. 5
Fig. 5
Within-twin-pair differences in all-cause mortality between the long-term leisure-time physical activity classes for (A) all twin pairs, (B) monozygotic (MZ) pairs and (C) dizygotic (DZ) pairs. The sedentary class was treated as the reference. Only twin pairs with information on LTPA and alive in 1990 were included in the analysis. Model 1 was adjusted for sex (female) and age at the between-twin-pair level. Model 2 was additionally adjusted for education, smoking and alcohol use at the within-twin pair level and Model 3 for body mass index at within-twin pair level. hOR, hazard odds ratio
Fig. 6
Fig. 6
Within-twin-pair differences in all-cause mortality between the long-term leisure-time physical activity classes for (A) all twin pairs, (B) monozygotic (MZ) pairs and (C) dizygotic (DZ) pairs after excluding twin pairs who reported prevalent cardiovascular disease (angina pectoris or myocardial infarction in 1975 or 1981). The sedentary class was treated as the reference. Only twin pairs with information on LTPA and alive in 1990 were included in the analysis. Model 1 was adjusted for sex (female) and age at the between-twin-pair level. Model 2 was additionally adjusted for education, smoking and alcohol use at the within-twin-pair level and Model 3 for body mass index at the within-twin-pair level
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