Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec 6;78(12):2045-2059.
doi: 10.1093/geronb/gbad128.

Associations Between Longitudinal Loneliness, DNA Methylation Age Acceleration, and Cognitive Functioning

Morgan Lynch  1 , Thalida Em Arpawong  2 , Christopher R Beam  1   2
Affiliations

Associations Between Longitudinal Loneliness, DNA Methylation Age Acceleration, and Cognitive Functioning

Morgan Lynch et al. J Gerontol B Psychol Sci Soc Sci. .

Abstract

Objectives: Loneliness may influence aging biomarkers related to cognitive functioning, for example, through accelerated DNA methylation (DNAm) aging.

Methods: In the present study, we tested whether six common DNAm age acceleration measures mediated the effects of baseline loneliness and five different longitudinal loneliness trajectories on general cognitive ability, immediate memory recall, delayed memory recall, and processing speed in 1,814 older adults in the Health and Retirement Study.

Results: We found that baseline loneliness and individuals who belong to the highest loneliness trajectories had poorer general cognitive ability and memory scores. Only DNAm age acceleration measures that index physiological comorbidities, unhealthy lifestyle factors (e.g., smoking), and mortality risk-mediated effects of baseline loneliness on general cognitive ability and memory functioning but not processing speed. These same DNAm measures mediated effects of the moderate-but-declining loneliness trajectory on cognitive functioning. Additionally, immediate and delayed memory scores were mediated by GrimAge Accel in the lowest and two highest loneliness trajectory groups. Total and mediated effects of loneliness on cognitive functioning outcomes were mainly accounted for by demographic, social, psychological, and physiological covariates, most notably self-rated health, depressive symptomatology, objective social isolation, and body mass index.

Discussion: Current findings suggest that DNAm biomarkers of aging, particularly GrimAge Accel, have promise for explaining the prospective association between loneliness and cognitive functioning outcomes.

Keywords: Cognition; DNA methylation; Epigenetic age; Loneliness; Longitudinal.

PubMed Disclaimer

Conflict of interest statement

None declared.

Figures

Figure 1.
Figure 1.
Multicategorical Mediation Model. Loneliness trajectory groups 1, 2, … , j refer to the different loneliness trajectory classes found in the Growth Mixture Models. DNAm AgeAccel2016 refers to Horvath Age Acceleration, Hannum Age Acceleration, Horvath (skin) Age Acceleration, DNAm PhenoAge Acceleration, GrimAge Acceleration, and Dunedin PoAm38 Acceleration. CF2016 refers to TICSm, immediate memory recall, delayed memory recall, and processing speed. Covariates include cohort, sex, race/ethnicity, APOE ε4 status, social isolation, current smoking status, depressive symptomatology, self-rated health, and BMI. The parameters a1, a2, … , aj−1, refer to the effect of each loneliness trajectory group on DNAm AgeAccel for j–1 groups (the largest latent class group was selected as the reference group). The parameter b refers to the direct effect of DNAm AgeAccel measure on the cognitive functioning outcome. The parameters c’1, c’2, … , c’j−1, refer to the adjusted direct effect of each loneliness trajectory group for j–1 groups on the cognitive outcome.
See this image and copyright information in PMC

References

    1. Adam, E. K., Hawkley, L. C., Kudielka, B. M., & Cacioppo, J. T. (2006). Day-to-day dynamics of experience—Cortisol associations in a population-based sample of older adults. Proceedings of the National Academy of Sciences of the United States of America, 103(45), 17058–17063. 10.1073/pnas.0605053103 - DOI - PMC - PubMed
    1. Akhter-Khan, S. C., Tao, Q., Ang, T., Itchapurapu, I. S., Alosco, M. L., Mez, J., Piers, R. J., Steffens, D. C., Au, R., & Qiu, W. Q. (2021). Associations of loneliness with risk of Alzheimer’s disease dementia in the Framingham Heart Study. Alzheimer’s & Dementia, 17(10), 1619–1627. 10.1002/alz.12327 - DOI - PMC - PubMed
    1. Austin, M. K., Chen, E., Ross, K. M., McEwen, L. M., Maclsaac, J. L., Kobor, M. S., & Miller, G. E. (2018). Early-life socioeconomic disadvantage, not current, predicts accelerated epigenetic aging of monocytes. Psychoneuroendocrinology, 97, 131–134. 10.1016/j.psyneuen.2018.07.007 - DOI - PubMed
    1. Awad, R., Shamay-Tsoory, S., & Palgi, Y. (2023). Fluctuations in loneliness due to changes in frequency of social interactions among older adults: A weekly based diary study. International Psychogeriatrics, 35(6), 293–303. 10.1017/S1041610223000133 - DOI - PubMed
    1. Beam, C. R., & Kim, A. J. (2020). Psychological sequelae of social isolation and loneliness might be a larger problem in young adults than older adults. Psychological Trauma, 12(S1), S58–S60. 10.1037/tra0000774 - DOI - PubMed

Publication types