Blood-based biological ageing and red cell distribution width are associated with prevalent Parkinson's disease: findings from a large Italian population cohort

Front Endocrinol (Lausanne). 2024 Apr 10:15:1376545. doi: 10.3389/fendo.2024.1376545. eCollection 2024.

Abstract

Background: Aging clocks tag the actual underlying age of an organism and its discrepancy with chronological age and have been reported to predict incident disease risk in the general population. However, the relationship with neurodegenerative risk and in particular with Parkinson's Disease (PD) remains unclear, with few discordant findings reporting associations with both incident and prevalent PD risk.

Objective: To clarify this relationship, we computed a common aging clock based on blood markers and tested the resulting discrepancy with chronological age (ΔPhenoAge) for association with both incident and prevalent PD risk.

Methods: In a large Italian population cohort - the Moli-sani study (N=23,437; age ≥ 35 years; 52% women) - we carried out both Cox Proportional Hazards regressions modelling ΔPhenoAge as exposure and incident PD as outcome, and linear models testing prevalent PD as exposure and ΔPhenoAge as outcome. All models were incrementally adjusted for age, sex, education level completed and other risk/protective factors previously associated with PD risk in the same cohort (prevalent dysthyroidism, hypertension, diabetes, use of oral contraceptives, exposure to paints, daily coffee intake and cigarette smoking).

Results: No significant association between incident PD risk (209 cases, median (IQR) follow-up time 11.19 (2.03) years) and PhenoAging was observed (Hazard Ratio [95% Confidence Interval] = 0.98 [0.71; 1.37]). However, a small but significant increase of ΔPhenoAge was observed in prevalent PD cases vs healthy subjects (β (Standard Error) = 1.39 (0.70)). An analysis of each component biomarker of PhenoAge revealed a significant positive association of prevalent PD status with red cell distribution width (RDW; β (SE) = 0.46 (0.18)). All the remaining markers did not show any significant evidence of association.

Conclusion: The reported evidence highlights systemic effects of prevalent PD status on biological aging and red cell distribution width. Further cohort and functional studies may help shedding a light on the related pathways altered at the organism level in prevalent PD, like red cells variability, inflammatory and oxidative stress mechanisms.

Keywords: Parkinson’s disease; PhenoAge; biological aging; inflammation; oxidative stress; red cell distribution width.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging* / blood
  • Biomarkers / blood
  • Cohort Studies
  • Erythrocyte Indices*
  • Female
  • Humans
  • Incidence
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Parkinson Disease* / blood
  • Parkinson Disease* / epidemiology
  • Prevalence
  • Risk Factors

Substances

  • Biomarkers

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The enrollment phase of the Moli-sani Study was supported by unrestricted research grants from the Pfizer Foundation (Rome, Italy), the Italian Ministry of University and Research (MIUR, Rome, Italy)—Programma Triennale di Ricerca, Decreto no.1588, and Instrumentation Laboratory, Milan, Italy. The follow-up phase of the Moli-sani Study (validation of incident cases) was partially supported the Italian Ministry of Health (PI LI, CoPI MB; grant no. PNRR-MAD-2022-12376167). The present analyses were supported by Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE8 – Project Age-It: “Ageing Well in an Ageing Society” [DM 1557 11.10.2022]. No funder had a role in study design, collection, analysis, interpretation of data, writing of the manuscript, and decision to submit this article for publication.