Accelerated Biological Aging in Patients with Degenerative Spine Diseases: The Impact of Modifiable Lifestyle Factors on Phenotypic Age.

Background: Aging is influenced by genetic, environmental, and lifestyle factors, and chronological age alone may fail to capture one's true biological aging. Degenerative spinal disease (DSD) is associated with accelerated health decline, which could manifest as an increased Phenotypic Age (PhenoAge).

Purpose: This study aimed to investigate the association between Phenotypic Age (PhenoAge) and degenerative spine disease (DSD) in a Japanese population using a cross-sectional analysis complemented by a follow-up analysis, while also exploring the impact of modifiable lifestyle factors on biological aging.

Design/setting: A cross-sectional design was employed using data from a large health examination program in Japan.

Patient sample: A total of 10,205 individuals who underwent health examinations formed the reference cohort. Separately, two distinct clinical cohorts were analyzed: an OA cohort of 306 patients with hip or knee osteoarthritis who underwent arthroplasty, and a DSD cohort of 397 patients with adult spinal deformity (ASD) or lumbar spinal stenosis (LSS) who also underwent surgery.

Outcome measures: PhenoAge was calculated using clinical biomarkers, and the difference between PhenoAge and chronological age was expressed as PhenoAgeAccel. Additional inflammatory and metabolic markers (e.g., CRP, WBC) were evaluated alongside lifestyle factors such as smoking status, body mass index, and physical activity.

Method: Propensity score matching was used to compare PhenoAge between patients and controls. Linear regression examined the influence of lifestyle factors on PhenoAgeAccel. A subgroup analysis assessed differences between ASD and LSS, as well as between hip OA and knee OA. Individuals re-examined in 2023 were followed to evaluate the 3-year change in PhenoAgeAccel.

Results: Japanese participants had a mean PhenoAgeAccel of -8.0 ± 4.0 years (p < 0.01, Cohen's d = 0.8). DSD patients showed a 4.2-year elevation in PhenoAge over controls, accompanied by higher CRP and WBC levels (both p < 0.01 Cohen's d = 0.65). Subgroup analyses revealed no significant differences in PhenoAge between ASD vs. LSS or hip OA vs. knee OA. Smoking (β = 0.6; p < 0.01) and obesity (β = 1.5; p < 0.01) raised PhenoAgeAccel, while physical activity lowered it (β = -0.2; p = 0.03). Non-risk individuals improved by -0.5 years, whereas risk individuals worsened by +0.5 years over three years.

Conclusion: These findings suggest that PhenoAge may serve as a more sensitive marker of biological aging in DSD patients, although the retrospective design and potential confounding variables warrant cautious interpretation.