Review Maps Dysfunctional Mitochondrial Pathways and Precision Therapy Targets in Bone Aging

Bone aging is a complex process characterized by metabolic declines that compromise skeletal homeostasis and lead to age-related bone diseases. Normal cellular metabolism, particularly in osteoblasts, osteocytes, and osteoclasts, is vital for maintaining bone health. Mitochondrial dysfunction acts as a central driver, impairing energy production, amplifying oxidative stress, and disrupting metabolic balance. This review aims to unravel these dysfunctional pathways to identify precision therapeutic targets.

This comprehensive review systematically synthesized current literature on the role of mitochondrial homeostasis in bone aging. Researchers analyzed studies focusing on aberrant mitochondrial kinetics, quality control, protein homeostasis, ATP production, and calcium dysregulation. The review aimed to identify how these dysfunctional pathways contribute to bone aging and to pinpoint potential targets for precision therapies, drawing insights from various preclinical and clinical studies.

The review found that mitochondrial dysfunction is a central driver of bone aging, characterized by impaired energy production, amplified oxidative stress, and disrupted metabolic balance. Key dysfunctional pathways identified include aberrant mitochondrial kinetics and quality control, dysfunctional protein homeostasis, and inhibited ATP production.

Dysregulation of calcium homeostasis and metabolic reprogramming were also highlighted as critical, interacting factors that impair mitochondrial function as a hub for biosynthesis and signal transduction. These interconnected issues collectively contribute to the decline in skeletal homeostasis observed in aging. The synthesis of evidence points towards specific molecular targets within these pathways that could be leveraged for future therapeutic interventions.