Age-related changes in the energy of human mesenchymal stem cells.

Mario Barilani,Andrey Y Abramov,Lorenza Lazzari,Roberta Piras,Plamena R Angelova,Christopher Lovejoy

doi:10.1002/jcp.30638

Abstract

Aging is a physiological process that leads to a higher risk for the most devastating diseases. There are a number of theories of human aging proposed, and many of them are directly or indirectly linked to mitochondria. Here, we used mesenchymal stem cells (MSCs) from young and older donors to study age-related changes in mitochondrial metabolism. We have found that aging in MSCs is associated with a decrease in mitochondrial membrane potential and lower NADH levels in mitochondria. Mitochondrial DNA content is higher in aged MSCs, but the overall mitochondrial mass is decreased due to increased rates of mitophagy. Despite the higher level of ATP in aged cells, a higher rate of ATP consumption renders them more vulnerable to energy deprivation compared to younger cells. Changes in mitochondrial metabolism in aged MSCs activate the overproduction of reactive oxygen species in mitochondria which is compensated by a higher level of the endogenous antioxidant glutathione. Thus, energy metabolism and redox state are the drivers for the aging of MSCs/mesenchymal stromal cells.

Highlights

Progress in medicine increased the life expectancy in most of the countries around the world
This is of particular interest, as telomere erosion is directly involved in the aging process
The issue of whether and to which extent aging influences mesenchymal stem cells (MSCs) properties has been raising interest for many years (Schimke et al, 2015). This area of research has the aim to investigate the usefulness of bone marrow harvest from old donors in the context of an aging western population and to assess the therapeutic potential of its cellular derivatives

Summary

| INTRODUCTION

Progress in medicine increased the life expectancy in most of the countries around the world. Cells were washed with HEPES‐ buffered salt solution and images of the fluorescence of the MCB‐glutathione (GSH) were acquired using a Zeiss 710 CLSM with excitation at 405 nm and emission at 435–485 nm. A total of 10 fields were screened, acquiring images from n = 2 technical replicates (two separate wells of a six‐well plate), to analyse for positive staining at least 50 cells for each MSC population (n = 5 aged MSC vs n = 5 juvenile MSC). The gene expression of p21, a crucial protein involved in cell cycle control, was found to be significantly higher in aged MSC than in juvenile MSC (Figure 1c). Telomere's length was determined, and a significant decrease was detected in aged MSC compared to juvenile MSC (Figure 1d) This is of particular interest, as telomere erosion is directly involved in the aging process.

| RESULTS

Findings

| DISCUSSION