Artistic depiction of epigenetics and biological aging with a clock, DNA strands, and a child standing near an hourglass.Researchers from the University of Helsinki and Tampere University in Finland have made a groundbreaking discovery linking childhood resilience to biological aging in adulthood. The study, part of the long-running Young Finns Study initiated in 1980, found that early resilience—the mental capacity to cope with adversity—may significantly slow down the biological aging process. This finding suggests that the impact of childhood resilience extends far beyond psychological well-being, potentially influencing the body’s aging at a cellular level. Unlike chronological age, which simply measures the passage of time, biological aging reflects the actual physical condition of the body and can be influenced by various factors, including, as this study suggests, early-life resilience.

This study is the first to track early resilience’s impact on aging at the molecular level, specifically looking at DNA methylation changes. This biological aging process, known as “epigenetic aging,” is influenced by factors like environment, lifestyle, and genetics. Using “epigenetic clocks,” scientists measure biological age by analyzing DNA methylation patterns. These clocks, which include the Hannum, Horvath, PhenoAge, GrimAge, and the recent DunedinPACE clocks, provide insights into how quickly an individual ages biologically. Unlike traditional aging measures, epigenetic clocks can highlight health risks and assess aging rates with greater precision.

“It was indeed interesting that the most consistent associations of resilience were found with AgeDevGrim and DunedinPACE. Those epigenetic clocks among the strongest predictors of mortality and ageing-related clinical conditions. It seems that those clocks are the most reliable in capturing the ageing-related signs of the body.”

– Dr. Aino Saarinen, Senior Author of this study, Department of Psychology and Logopedics, University of Helsinki, Finland.

Epigenetic Aging and Epigenetic Clocks

Epigenetic aging refers to the changes in DNA methylation patterns that occur as an organism ages. DNA methylation is a process by which methyl groups are added to specific sites on DNA molecules, affecting gene expression without altering the underlying genetic sequence. These methylation patterns can be influenced by various factors, including environmental exposures, lifestyle choices, and genetic predisposition.

As we age, certain DNA methylation patterns change in predictable ways, allowing researchers to develop “epigenetic clocks” that can estimate an individual’s biological age based on their methylation profile. These clocks have proven to be remarkably accurate in predicting chronological age and, more importantly, in assessing biological age, which may differ from chronological age due to various health and lifestyle factors.

First-Generation Epigenetic Clocks

The first generation of epigenetic clocks includes the Hannum clock and the Horvath clock. These clocks were developed by regressing DNA methylation levels at specific CpG sites (regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide) against chronological age.

Hannum Clock: Created by Dr. Gregory Hannum, it is a single-tissue calculator based on 71 CpG sites in human blood DNA. While highly accurate in predicting lifespan, it is primarily designed for use with adult blood samples and may not be suitable for children or other tissue types.

Horvath Clock: Developed by Dr. Steve Horvath, this multi-tissue predictor is based on 353 CpG sites. It has the advantage of being applicable across various tissue types and ages, including children. It has been widely used in research and has shown strong correlations with age-related health outcomes.

Second-Generation Epigenetic Clocks

The second generation of epigenetic clocks incorporated additional health biomarkers and phenotypes into their age predictions, aiming to provide a more comprehensive assessment of biological aging.

PhenoAge Clock: Developed by Levine et al., it is based on 513 age-related CpG sites and incorporates various clinical measures of phenotypic age. This clock has shown a strong association with mortality risk, with a one-year increase in DNAm PhenoAge corresponding to a 4.5% increase in all-cause mortality risk.

GrimAge Clock: Created by Lu et al., it is composed of seven DNA methylation-based plasma protein indicators and a measure of smoking pack-years. This clock has been particularly successful in predicting all-cause mortality and has outperformed previous DNA methylation-based predictors in estimating lifespan.

Third-Generation Epigenetic Clock

The latest development in epigenetic clocks is the third-generation DunedinPACE clock, which represents a significant advancement in the field.

DunedinPACE Clock: The DunedinPACE (Pace of Aging Computed from the Epigenome) clock was developed based on within-individual changes in 19 indicators of organ-system integrity, including measures such as BMI, leukocyte telomere length, and HDL cholesterol. This clock aims to capture the pace of biological aging more accurately by focusing on longitudinal changes in physiological function rather than solely on chronological age or cross-sectional health markers.

Study Design and Participants

The Young Finns study included 986 participants, assessing resilience through parent-reported evaluations of cooperation, focus, and helpfulness from ages 3 to 18. Epigenetic aging was then evaluated in adulthood using the following advanced clocks:

  • AgeDevGrim: A measure of biological aging that integrates multiple health indicators and is strongly associated with mortality risk.
  • DunedinPACE: A biomarker of the pace of aging that captures how quickly an individual’s biological systems are aging over time.
  • AgeDevHorvath: An epigenetic clock based on DNA methylation patterns that estimates biological age relative to chronological age.
  • AgeDevHannum: A DNA methylation-based aging measure focused on age-related changes that correlate with various health risks and mortality.

Results

“First, the results indicate that early resilience factors do have predictive power that extends into adulthood. Thus, interventions supporting children’s and adolescents’ resilience factors might protect them against accelerated ageing.

Second, we found that very high levels of psychological strength or social satisfaction may not have an additive protective effect against epigenetic ageing. Thus, extreme high levels of psychological resilience may possibly have ‘biological costs’ and not always ‘more is better.’ This aligns with previous studies reporting that extremely high levels of social activities may relate to elevated stress levels in some populations.”

Dr. Aino Saarinen, Senior Author of this study, Department of Psychology and Logopedics, University of Helsinki, Finland.

The findings revealed that high early resilience was generally associated with lower levels of epigenetic aging, particularly AgeDevGrim and DunedinPACE, which are considered strong indicators of mortality and age-related conditions. However, associations with AgeDevHorvath, AgeDevHannum, and AgeDevPheno were less consistent. Key insights include:

  1. Overall Early Resilience: Higher total resilience scores predicted reduced levels of AgeDevGrim, AgeDevPheno, and DunedinPACE, even after accounting for genetic risk and early family environment. In models fully adjusted for adulthood factors, the association persisted primarily for AgeDevGrim.
  2. Domain-Specific Findings:
    • Psychological Strength and Social Satisfaction: Showed non-linear relationships with AgeDevGrim, suggesting that while moderate levels may benefit biological aging, very high levels do not confer additional advantages.
    • Leisure Time Activities: Associated with slower aging across multiple measures, though the significance of this finding diminished after full adjustment.
    • Responsible Health Behaviors: Demonstrated associations with several epigenetic aging indicators, including AgeDevHannum and DunedinPACE.
    • School Career: Consistently linked to favorable epigenetic aging outcomes across different clocks.
  3. Longitudinal Analysis: In a subset of participants with data from 1986, high resilience was predictive of lower AgeDevGrim over a 25-year period, but primarily in individuals who exhibited higher baseline epigenetic age, indicating a potentially greater impact in those at higher risk for accelerated aging.

 

One question arising from this study is why educational or career-oriented achievements might significantly influence biological aging. Dr. Aino Saarinen responded:

“To our knowledge, this study was the first on that topic; thus, we do not have any firm explanations yet. Nevertheless, educational achievements are known to enhance subjectively experienced quality of life and other indicators of psychological well-being. Thus, we speculate that educational success may have general health-promoting effects that, in turn, may e.g. reduce stress levels and relate to decelerated ageing.”

Limitations

While the findings are promising, the study has limitations:

  1. The longitudinal subsample was small, limiting the power to detect long-term effects.
  2. The lack of follow-up resilience measures during adulthood restricts understanding of how changes in resilience over time influence aging.
  3. The potential for residual confounding despite comprehensive adjustment for covariates.

Conclusion

This study provides evidence that early psychosocial resilience is linked to slower epigenetic aging, highlighting the importance of fostering resilience in childhood and adolescence. These findings suggest that public health strategies focusing on enhancing psychosocial resources early in life may contribute to healthier aging trajectories across populations. Further research is needed to replicate these findings in larger samples and to explore the mechanisms through which resilience may mitigate biological aging.

For Further Reading

  1. Early resilience and epigenetic ageing: Results from the prospective Young Finns Study with a 31-year follow-up.
  2. Epigenetic Clocks: In Aging-Related and Complex Diseases.
  3. A Targeted Epigenetic Clock for the Prediction of Biological Age.
  4. Epigenetic clock: A promising biomarker and practical tool in aging.
  5. DNA methylation GrimAge strongly predicts lifespan and healthspan.
  6. “GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorder.

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