A Single-Cell Metabolic Profiling Characterizes Human Aging via SlipChip-SERS.

Fugang Liu, Jiaqing Liu, Yang Luo, Siyi Wu, Xu Liu, Haoran Chen, Zhewen Luo, Haitao Yuan, Feng Shen, Fangfang Zhu, Jian Ye

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China. · pubmed

Paper

Abstract

Metabolic dysregulation is a key driver of cellular senescence, contributing to the progression of systemic aging. The heterogeneity of senescent cells and their metabolic shifts are complex and unexplored. A microfluidic SlipChip integrated with surface-enhanced Raman spectroscopy (SERS), termed SlipChip-SERS, is developed for single-cell metabolism analysis. This SlipChip-SERS enables compartmentalization of single cells, parallel delivery of saponin and nanoparticles to release intracellular metabolites and to realize SERS detection with simple slipping operations. Analysis of different cancer cell lines using SlipChip-SERS demonstrated its capability for sensitive and multiplexed metabolic profiling of individual cells. When applied to human primary fibroblasts of different ages, it identified 12 differential metabolites, with spermine validated as a potent inducer of cellular senescence. Prolonged exposure to spermine can induce a classic senescence phenotype, such as increased senescence-associated β-glactosidase activity, elevated expression of senescence-related genes and reduced LMNB1 levels. Additionally, the senescence-inducing capacity of spermine in HUVECs and WRL-68 cells is confirmed, and exogenous spermine treatment increased the accumulation and release of H

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Research summary

The paper investigates metabolic dysregulation as a driver of cellular senescence, which is a key aspect of aging. It employs innovative technology (SlipChip-SERS) to analyze single-cell metabolism, providing insights into the metabolic shifts associated with aging. While the findings contribute to understanding the mechanisms of aging, the impact is limited as it primarily focuses on metabolic profiling rather than directly addressing interventions for lifespan extension or reversing aging processes.

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