Quantitative proteomics reveals coordinated changes in the proteome during replicative senescence

N. Da Silva Fernandes, F. Kielisch, A. Fulzele, S. Karunanithi, J. F. Graf, J. X. Chen, C. Behl, H. D. Ulrich

1. 01

   Proteome changes during replicative senescence are coordinated, not piecemeal

2. 02

   Widespread protein depletion on chromatin is a defining feature

3. 03

   Cytoplasmic translation machinery is depleted; mitochondrial proteins become more insoluble

4. 04

   Autophagic and proteasome activity is compromised, with remodelled ubiquitin linkages and depleted E3 ligases

5. 05

   A distinctive senescent signature emerges, shaped by the proteostasis network and separable from other pathophysiological cell states

Study Design

Preclinical mechanistic study

Sample Size

Not reported

Study Duration

Not reported

Methodology

Mass spectrometry-based quantitative proteomics applied at multiple levels (total proteome, chromatin-associated fraction, solubility and ubiquitin-linkage profiling) across the temporal progression of replicative senescence in cultured human cells, benchmarked against other pathophysiological cellular states.

Limitations

In vitro replicative senescence in cultured cells only - no in vivo, tissue or human data. Replicative senescence may not represent therapy-induced, oncogene-induced or stress-induced senescent states. It is a resource describing a signature, not evidence that any senolytic or senomorphic agent acts through the proteostasis axis, and it has not been developed into a usable clinical assay.