An innovative method of isolating 'young' stem cells still present in old mice has been developed during a study that also highlights how the activity of mitochondria plays a central role in stem cell 'fitness' rather than age.
According to a collaborative study between Lund Stem Cell Centre, Sweden and University College London, there is clinical potential of targeting mitochondrial activity for the treatment of age associated blood disease. Ageing leads to a decrease in blood stem cells' ability to produce adequate levels of mature blood cells. This can lead to an increased risk of blood disorders such as anaemia and cancer.
'We began by comparing the mitochondrial activity of stem cells from old and young mice.' explains Dr Els Mansell, a postdoctoral researcher and first author of the study. 'To do this we looked at mitochondrial membrane potential, MMP for short, reflecting the electrical potential and proton gradient of mitochondria.'
The study presents a conceptualised view on ageing in two forms: chronological age and physiological age. The former, referring to the actual age of the organism, hence all stem cells within an organism will share the same chronological age. Physiological age refers to an age-linked performance characteristic. Thus, cells that share the same chronological age could have different physiological ages.
The study, published in Cell Stem Cell, revealed, there is a general decrease in mitochondrial activity of stem cells with age but they did discover a small population of (chronologically) aged stem cells that had an MMP similar to that of young stem cells. This population of old stem cells exhibited a gene expression profile that was very similar to that of young stem cells.
'We then performed transplantation studies with stem cells isolated from aged mice treated with mitoquinol (mito-Q), a drug that increases MMP,' explains Dr Mansell.
The treated mito-Q, aged stem cells, behave like young stem cells. The researchers speculate the clinical possibility of targeting mitochondrial activity for the treatment of age related blood disease. Supplementation with mito-Q, in both middle aged and old mice, could prevent, and even reverse, the imbalance of mature blood cells and anaemia associated with ageing.
'Our findings prove that MMP is a novel indicator of the physiological age of stem cells, regardless if they are from young or old mice, and importantly, that the MMP of stem cells is a novel therapeutic target that can directly impact stem cell function,' concluded Dr Mansell.