Biology subjects

Shinhmar, H.

Publications and source records attributed to Shinhmar, H..

3 recordsLinked to original sources

bioRxiv2022

Mitochondrial decline in the ageing old world primate retina: little evidence for difference between the centre and periphery

Mitochondrial decline is a key feature of ageing. The retina has more mitochondria than any other tissue and ages rapidly. To understand human retinal ageing it is critical to examine old world primates that have similar visual systems to humans, and do so across central and peripheral regions, as there is evidence for early central decline. Hence, we examine mitochondrial metrics in young and ageing Macaca fascicularis retinae. In spite of reduced ATP with age, primate mitochondrial complex activity did not decline. But mitochondrial membrane potentials were reduced significantly, and concomitantly, mitochondrial membrane permeability increased. The mitochondrial marker Tom20 declined significantly, consistent with reduced mitochondria number, while VDAC, a voltage dependent anion channel and diffusion pore associated with apoptosis increased significantly. In spite of these clear age-related changes, there was almost no evidence for regional differences between the centre and the periphery. Primate cones do not die with age, but many showed marked structural decline with vacuous spaces in proximal inner segments normally occupied by endoplasmic reticulum (ER), that regulate mitochondrial autophagy. In many peripheral cones, ER was displaced by the nucleus that transposed across the outer limiting membrane and could become embedded in mitochondrial populations. These data are consistent with significant changes in retinal mitochondria in old world primate ageing but provide little if any evidence that aged central mitochondria suffer more than those in the periphery.

neuroscience↗

bioRxiv2021

Long wavelength light that improves aged mitochondrial function selectively increases cytokine expression in serum and the retina

Aged mitochondrial function can be improved with long wavelength light exposure. This reduces cellular markers of inflammation and can improve system function from fly though to human. Here, we ask what impact 670nm light has on cytokine expression using a 40 cytokine array in blood serum and retina in C57Bl6 mice. There was a relatively uniform increase in cytokine expression between 3 and 12 months of age in serum and retina. 670nm exposure was delivered daily for a week in 12 month old mice. This shifted patterns of cytokine expression in both serum and retina inducing a selective increase with some in serum increasing >5 fold. Changes in retina were smaller. In serum there were major increases in IL-7, 6, 13, 16 and 23, also in TNF- and CXCL 9 and 10. In retina the increases were found mainly in some IL (interleukins) and CXCLs (chemokines). A few cytokines were reduced by light exposure. Changes in serum cytokines implies that long wavelengths impacts systemically even to unexposed tissues deep in the body. In the context of wider literature, increased cytokine expression may be protective. However, their upregulation by light merits further analysis as cytokines upregulation can also be negative.

molecular biology↗

bioRxiv2021

The morning burst: Shifting daily patterns of ATP production in Drosophila and temporal windows for their improvement in ageing

Mitochondria produce energy for cell function via adenosine triphosphate (ATP) and are regulated by a molecular 24h clock. Here we use Drosophila melanogaster to reveal shifts in whole animal ATP production over 24h, showing a marked peak in the morning that declines around midday and remains low from then through to the following morning. Mitochondrial membrane potential and ATP production has been shown previously to improve after long wavelength exposure, but apparently not at all times. Hence, to explore this further we exposed flies to 670nm at different times. Exposures between 08.00 and 11.00 resulted in a significant increase in ATP, while exposures at other times had no effect. Within the morning window, not all times were equally effective, however, 670nm exposure mid-morning when ATP production was maximal did not increase ATP, possibly because mitochondria lacked spare capacity at this time. Hence, in the morning there is a complex dynamic relationship between long wavelength light and mitochondria. Mitochondrial function and the influence of long wavelengths are conserved across species from fly to human, and determining the time points for light administration to improve function in ageing and disease is of key importance. Our data progress this search and reveal the outline of these times.

physiology↗