Journal of Proteome Research · Nov 6, 2026

Mapping the Metabolic Landscape of Aging: Advances in Spatial Metabolomics for Deciphering Heterogeneity in Age-Related Diseases

By Zhang G, Hu F, Deng Y et al.

Aging is marked by a profound paradox, and rising life expectancy is not matched by an equivalent extension of healthspan. The core of this disconnect lies in systemic metabolic dysregulation, a hallmark of aging that traditional metabolomics, limited to tissue homogenates, fails to capture owing to its inherent spatial complexity. This review addresses this critical gap by systematically elucidating how spatial metabolomics is transforming geriatric medicine. We first outline how this technology maps organ- and cell-specific metabolic landscapes, revealing that aging disrupts metabolic networks in highly heterogeneous, region-specific patterns. We then detail its mechanistic role in deciphering the metabolic origins of age-related diseases, from the toxic microenvironments surrounding amyloid plaques to the metabolic drivers of plaque instability. Furthermore, we explore its application in evaluating the spatial pharmacodynamics of antiaging interventions and discuss the path to clinical translation through integration with spatial multiomics and artificial intelligence. By shifting the paradigm from homogenate biology to spatial biology, this review establishes spatial metabolomics as an indispensable framework for deconvoluting the heterogeneity of aging. It provides the methodological foundation to map the healthy aging atlas and enables a move from simply understanding aging to actively shaping its trajectory through precision diagnostics and targeted interventions.

doi.org/10.1021/acs.jproteome.6c00730PubMed 42992917Mechanisms