Biologically Younger Individuals, as Identified by MARK-AGE Biological Age Scores, Display a Distinct Favourable Blood Chemistry Profile Regardless of Age.

The MARK-AGE Study derived mathematical formulas yielding a 'bioage score' based on sets of 10 biomarkers each for females and males from a European population study.

• The study included 3300 subjects aged 35–74 years.
• A total of 362 clinical-chemistry, genetic, cellular, or molecular biomarkers were analysed per subject.
• Both statistical models and machine learning were used to derive the bioage score formulas.
• Separate formulas were developed for females and for males, each using 10 biomarkers.

Subjects with Down Syndrome and smoking females are biologically older according to the MARK-AGE bioage scores.

• Down Syndrome subjects showed a positive age difference (biological age exceeding chronological age).
• Smoking females also displayed a positive age difference, indicating accelerated biological ageing.
• These findings were identified using the MARK-AGE biomarker-based biological age scoring system.
• Age difference was defined as biological age minus chronological age.

Postmenopausal females taking hormone replacement therapy (HRT) are biologically younger according to the MARK-AGE bioage scores.

• HRT-using postmenopausal females displayed a negative age difference (biological age less than chronological age).
• This finding was identified using the same MARK-AGE biomarker-based scoring system applied to the broader population.
• The result suggests a biological age-reducing association with hormone replacement therapy in postmenopausal women.

Age difference (biological minus chronological age) is linearly correlated with levels of HDL, 25-hydroxy-Vitamin D, and CD3+ CD4+/CD45+ ratio, such that biologically younger subjects display values favourable to good health.

• HDL cholesterol, 25-hydroxy-Vitamin D, and the CD3+ CD4+/CD45+ T-cell ratio were all correlated with age difference but not with chronological age alone.
• Biologically younger subjects (negative age difference) showed higher levels of these markers, which are considered favourable for health.
• These correlations were identified as independent of chronological age, representing a distinct biological ageing signature.

Glucose and HbA1c are correlated with chronological age but not with age difference, representing a different category of ageing-related markers.

• Glucose and HbA1c showed significant correlation with chronological age in the MARK-AGE cohort.
• These markers did not show significant linear correlation with age difference (biological minus chronological age).
• This pattern contrasts with HDL, 25-hydroxy-Vitamin D, and CD3+ CD4+/CD45+ ratio, which correlated with age difference but not chronological age.
• The authors interpret this dichotomy as potentially indicating different roles: 'drivers of the ageing process versus bystanders of ageing.'

A dichotomy exists between biomarkers that correlate with age difference versus those that correlate with chronological age, suggesting different mechanistic roles in ageing.

• Markers correlated with age difference (HDL, 25-hydroxy-Vitamin D, CD3+ CD4+/CD45+ ratio) may represent 'drivers of the ageing process.'
• Markers correlated with chronological age but not age difference (glucose, HbA1c) may represent 'bystanders of ageing.'
• This distinction was identified using the MARK-AGE biological age scoring framework across 3300 subjects.