# Differential Responses to Aging Among the Transcriptome and Proteome of Mesenchymal Progenitor Populations

## TL;DR

This study finds that aging affects the gene activity of stem cells, but these changes don't always show up in the proteins made by the cells.

## Contribution

The study reveals distinct transcriptomic changes in aged mesenchymal progenitor cells that are not consistently reflected in their proteome.

## Key findings

- Older mesenchymal progenitor cells showed suppressed proliferation and differentiation in transcriptomic data.
- Transcriptomic changes in older cells suggest a proinflammatory immune shift not mirrored in proteomic data.
- Transcriptomic shifts in COP and ADSC cells were not consistently reflected in proteomic profiles.

## Abstract

The biological aging of stem cells (exhaustion) is proposed to contribute to the development of a variety of age-related conditions. Despite this, little is understood about the specific mechanisms which drive this process. In this study, we assess the transcriptomic and proteomic changes in 3 different populations of mesenchymal progenitor cells from older (50–70 years) and younger (20–40 years) individuals to uncover potential mechanisms driving stem cell exhaustion in mesenchymal tissues. To do this, we harvested primary bone marrow mesenchymal stem and progenitor cells (MPCs), circulating osteoprogenitors (COP), and adipose-derived stem cells (ADSCs) from younger and older donors, with an equal number of samples from men and women. These samples underwent RNA sequencing and label-free proteomic analysis, comparing the younger samples to the older ones. There was a distinct transcriptomic phenotype in the analysis of pooled older stem cells, suggestive of suppressed proliferation and differentiation; however, these changes were not reflected in the proteome of the cells. Analyzed independently, older MPCs had a distinct phenotype in both the transcriptome and proteome consistent with altered differentiation and proliferation with a proinflammatory immune shift in older adults. COP cells showed a transcriptomic shift to proinflammatory signaling but no consistent proteomic phenotype. Similarly, ADSCs displayed transcriptomic shifts in physiologies associated with cell migration, adherence, and immune activation but no proteomic change with age. These results show that there are underlying transcriptomic changes with stem cell aging that may contribute to a decline in tissue regeneration. However, the proteome of the cells was inconsistently regulated.