Multimodal Technology-Driven aging Research: Decoding the Mitochondria‒Pyroptosis axis in muscle atrophy and cognitive decline.

Abstract

Population aging drives a parallel increase in muscle atrophy and cognitive decline, two major causes of disability in older adults. Mitochondrial dysfunction and chronic inflammation are core drivers of aging, with pyroptosis serving as a critical link between them. However, conventional single‑technique approaches capture only fragmented, static information and fail to bridge molecular events with whole‑organism phenotypes. This review introduces a unique integrative perspective that weaves established multimodal technologies ranging from molecular interaction analysis and absolute quantification to cellular metabolic and electrophysiological recordings, tissue clearing and laser microdissection, and finally to in vivo imaging and body composition analysis into a coherent, cross‑scale chain of evidence. By applying this paradigm to the mitochondria‑pyroptosis axis, we reveal how oxidative mitochondrial DNA enhances NLRP3 binding, how aged cells exhibit metabolic vulnerability and electrophysiological susceptibility, how pyroptotic hotspots form with spatial heterogeneity in tissues, and how pyroptosis signals quantitatively correlate with the decline in muscle mass and cognitive function. The core contribution of this review is the methodological framework of multimodal integration that enables causal tracing from molecular triggers to functional outcomes. This paradigm offers a transferable strategy for dissecting complex aging mechanisms and provides a theoretical foundation for targeting the mitochondria‑pyroptosis axis in precision anti‑aging interventions.