Age decreases mitochondrial motility and increases mitochondrial size in vascular smooth muscle : Smooth muscle mitochondrial shape and motility changes with age

Chalmers, Susan and Saunter, Christopher and Girkin, John M. and McCarron, John G. (2016) Age decreases mitochondrial motility and increases mitochondrial size in vascular smooth muscle : Smooth muscle mitochondrial shape and motility changes with age. Journal of Physiology, 594 (15). 4283–4295. ISSN 0022-3751

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    Abstract

    Mitochondrial function, motility and architecture are each central to cell activities; age-associated mitochondrial dysfunction may contribute to vascular disease. Mitochondrial changes in ageing remain ill-defined, however, due to challenges of imaging in native cells. We determined the structure of mitochondria in live native cells, demarcating boundaries of individual organelles by inducing stochastic “flickers” of membrane potential, recorded as fluctuations in potentiometric fluorophore intensity (Flicker-assisted Localization Microscopy, FaLM). In freshly-isolated myocytes from rat cerebral resistance arteries, FaLM showed a range of mitochondrial X-Y-areas in both young adult (3 months; 0.05-6.58 µm2) and aged rats (18 months; 0.05-13.4 µm2). In cells from young animals most mitochondria were small (mode area 0.051 µm2) compared to aged animals (0.710 µm2). Cells from older animals contained a subpopulation of highly-elongated mitochondria (5.3% were >2 µm long, 4.2% had a length:width ratio >3) that was rare in younger animals (0.15% of mitochondria >2 µm long, 0.4% had length:width ratio >3). The extent of mitochondrial motility also varied. 1/811 mitochondria observed moved slightly (~0.5 µm) in myocytes from older animals, whereas in the younger animals directed and Brownian-like motility occurred regularly (215/1135 mitochondria moved within 10 min, up to 12 µm distance). Mitochondria positioned closer to the cell periphery were more likely to move. In conclusion, cerebral vascular myocytes from young rats contained small, motile mitochondria. In aged rats mitochondria were larger, immobile and could be highly-elongated. These age-associated alterations in mitochondrial behaviour may contribute to alterations in cell signalling, energy supply or the onset of proliferation.