Differential mitochondrial bioenergetics and cellular resilience in astrocytes, hepatocytes, and fibroblasts from aging baboons.
Daniel A AdekunbiHillary Fries HuberCun LiPeter W NathanielszLaura A CoxAdam B SalmonPublished in: bioRxiv : the preprint server for biology (2024)
Biological resilience, broadly defined as ability to recover from acute challenge and return to homeostasis, is of growing importance to the biology of aging. At the cellular level, there is variability across tissue types in resilience and these differences likely to contribute to tissue aging rate disparities. However, there are challenges in addressing these cell-type differences at regional, tissue and subject level. To address this question, we established primary cells from aged male and female baboons between 13.3-17.8 years spanning across different tissues, tissue regions, and cell types including: (1) fibroblasts from skin and from heart separated into left ventricle (LV), right ventricle (RV), left atrium (LA) and right atrium (RA), (2) astrocytes from the prefrontal cortex and hippocampus and (3) hepatocytes. Primary cells were characterized by their cell surface markers and their cellular respiration assessed with Seahorse XFe96. Cellular resilience was assessed by modifying a live-cell imaging approach we previously reported that monitors proliferation of dividing cells following response and recovery to oxidative (50µM-H 2 O 2 ), metabolic (1mM-glucose) and proteostasis (0.1µM-thapsigargin) stress. We noted significant differences even among similar cell types that are dependent on tissue source and the diversity in cellular response is stressor specific. For example, astrocytes were more energetic and exhibited greater resilience to oxidative stress (OS) than both fibroblasts and hepatocytes. RV and RA fibroblasts were less resilient to OS compared with LV and LA respectively. Skin fibroblasts were less impacted by proteostasis stress compared to astrocytes and cardiac fibroblasts. Future studies will test the functional relationship of these outcomes to age and developmental status of donors as potential predictive markers.
Keyphrases
- oxidative stress
- induced apoptosis
- climate change
- extracellular matrix
- mycobacterium tuberculosis
- prefrontal cortex
- social support
- pulmonary artery
- single cell
- rheumatoid arthritis
- liver injury
- signaling pathway
- pulmonary hypertension
- cell surface
- cell cycle arrest
- gene expression
- cell therapy
- dna damage
- drug induced
- left ventricular
- stem cells
- coronary artery
- type diabetes
- blood pressure
- photodynamic therapy
- mass spectrometry
- cell death
- ischemia reperfusion injury
- skeletal muscle
- pi k akt
- congenital heart disease
- systemic sclerosis
- subarachnoid hemorrhage
- ankylosing spondylitis
- left atrial appendage
- blood brain barrier
- cerebral ischemia
- bone marrow
- heat shock protein
- glycemic control
- human health