Work

Acid–Base Dysregulation Links Aging Metabolism to Frailty

Year: 2026

Type: article

Abstract: Frailty denotes a state of high vulnerability and, as proposed by Fried and colleagues, arises from "energetic collapse" across multiple physiological systems, in which altered energy metabolism undermines resilience. We suggest that dysregulation of acid-base balance represents a critical yet underappreciated mechanism driving this collapse. With aging, cumulative stress burden diminishes the capacity for intracellular and extracellular acid buffering, renal acid excretion and ventilatory reserve, leading to impaired pH homeostasis, reduced mitochondrial ATP production, and declining cellular and organismal efficiency. Skeletal muscle, bone, liver, and kidney cooperate to mobilize the base reserves and redirect amino acid metabolism to enhance renal acid elimination. But this adaptation occurs at the expense of musculoskeletal integrity-a hallmark of aging. The shrinking iceberg metaphor illustrates frailty progression. Repeated stressors erode the acid buffer and energy reserve. Incorporating acid-base dysregulation into frailty models highlights new therapeutic targets-including diet, exercise and buffering strategies to preserve reserve and delay frailty progression.

Source: Aging Cell

DOI: 10.1111/acel.70466

Authors: Wan‐Hui Liao, Wolfgang Langhans, Maciej Henneberg

Institutions: Mackay Memorial Hospital, ETH Zurich, University of Zurich, Adelaide University, The University of Adelaide

Language: English

Topic: Renal function and acid-base balance

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,790