Acid-Base Dysregulation Links Aging Metabolism to Frailty

Area of Science:

• Gerontology
• Physiology
• Biochemistry

Background:

• Frailty is a state of vulnerability linked to "energetic collapse" across physiological systems.
• Altered energy metabolism and reduced resilience are key features of frailty.
• The role of acid-base balance in frailty progression is underappreciated.

Purpose of the Study:

• To propose that dysregulation of acid-base balance is a critical mechanism driving frailty.
• To explore how aging impacts acid buffering, renal acid excretion, and pH homeostasis.
• To highlight potential therapeutic targets for frailty based on acid-base balance.

Main Methods:

• Conceptual review and synthesis of existing literature on frailty and acid-base physiology.
• Analysis of the physiological consequences of impaired pH homeostasis with aging.
• Illustration of frailty progression using the "shrinking iceberg" metaphor.

Main Results:

• Aging diminishes the body's capacity for acid buffering and acid excretion, impairing pH homeostasis.
• Impaired pH homeostasis leads to reduced mitochondrial ATP production and decreased cellular efficiency.
• Adaptations to maintain acid-base balance, such as mobilizing base reserves, compromise musculoskeletal integrity.

Conclusions:

• Dysregulation of acid-base balance is a critical, underappreciated mechanism in frailty.
• Therapeutic strategies targeting acid-base balance (diet, exercise, buffering) could preserve physiological reserve and delay frailty.
• Integrating acid-base dysregulation into frailty models opens new avenues for intervention.