Disuse rescues the age-impaired adaptive response to external loading in mice

Area of Science:

• Bone biology and mechanotransduction
• Skeletal adaptation to mechanical stimuli
• Gerontology and age-related bone loss

Background:

• Age-related bone loss is associated with reduced adaptation to mechanical loading.
• In young mice, reduced habitual activity enhances bone's response to mechanical loading.
• The study investigates if this effect extends to aged mice.

Purpose of the Study:

• To determine if modulating habitual activity can restore aged bone's response to mechanical loading.
• To investigate the role of habitual strain in age-related bone adaptation.
• To assess the potential of targeted mechanical stimuli in aged bone.

Main Methods:

• Sciatic neurectomy (SN) was used to reduce habitual loading in aged mice.
• The osteogenic response to mechanical loading was assessed using micro-computed tomography (μCT) and dynamic histomorphometry.
• Experiments involved both single peak loads and a range of load magnitudes.

Main Results:

• SN in aged mice significantly increased the periosteal osteogenic response to loading compared to controls.
• Reducing habitual activity abrogated age-related differences in bone's response to peak strain magnitude.
• Aged bone, when subjected to appropriate stimuli, demonstrated a robust osteogenic response.

Conclusions:

• The age-related decline in bone's osteogenic responsiveness is likely due to 'strain averaging' from habitual loading, not cellular dysfunction.
• Modulating habitual activity can rescue the mechanical responsiveness of aged bone.
• Findings suggest that in humans, gentle exercise might diminish the benefits of more vigorous activity.