Transcriptomic and metabolomic changes might predict frailty in SAMP8 mice

Area of Science:

• Gerontology
• Neuroscience
• Metabolomics

Background:

• Frailty is a multi-dimensional geriatric syndrome linked to reduced resilience and increased risk of Alzheimer's disease (AD).
• Frailty is considered a reversible condition, highlighting the need for early biomarkers for timely prediction and prevention.
• Senescence-Accelerated Mouse Prone-8 (SAMP8) mice serve as a preclinical model for studying frailty and its progression.

Purpose of the Study:

• To investigate the transcriptional and metabolic changes associated with frailty in SAMP8 mice.
• To identify early biomarkers for frailty that may predict dementia development.
• To characterize the cognitive, motor, structural, and neuropathological aspects of frailty in SAMP8 mice at different ages.

Main Methods:

• Characterization of SAMP8 mice at 2.5, 6, and 9 months of age, assessing cognitive, motor, structural, and neuropathological parameters.
• Transcriptional analysis of brain tissue to identify genetic signatures.
• Plasma metabolomic analysis to detect metabolic alterations.

Main Results:

• SAMP8 mice exhibited memory deficits, muscle weakness, and motor impairment starting at 2.5 months of age.
• Functional deficits were associated with neurodevelopmental issues, including reduced neuronal density and glial cell loss.
• Transcriptomics revealed distinct genetic signatures in SAMP8 mice by 6 months, while plasma metabolomics identified lower acylcarnitines and lipids in SAMP8 mice from 2.5 months onwards, correlating with functional and neuropathological findings.

Conclusions:

• Specific genetic alterations in the brain and metabolic changes in plasma can serve as early indicators of frailty.
• These findings suggest potential biomarkers for early assessment of frailty, paving the way for clinical investigations into dementia prevention.
• The study underscores the utility of the SAMP8 mouse model for understanding the pathogenesis of frailty and its link to neurodegenerative diseases.