Mitochondrial Function, Mobility and Lifespan Are Improved in Drosophila melanogaster by Extracts of 9-cis-ß-Carotene from Dunaliella salina.

Carotenoids are implicated in alleviating ageing and age-related diseases in humans. While data from different carotenoids are mixed in their outcomes, those for 9-cis-ß-carotene indicate general positive effects, although basic data on its biological impact are limited. Here, we show that supplementation with 9-cis-ß-carotene in ageing Drosophila melanogaster improved mitochondrial function in terms of ATP production and whole-body respiration and extended mean lifespan. It also resulted in improved mobility. These data provide a potential biological rational for the beneficial effects of dietary supplementation with 9-cis-ß-carotene. These effects may be based on the maintenance of a sound mitochondrial function.

Photobiomodulation reduces gliosis in the basal ganglia of aged mice.

This study explored the effects of long-term photobiomodulation (PBM) on the glial and neuronal organization in the striatum of aged mice. Mice aged 12 months were pretreated with PBM (670 nm) for 20 minutes per day, commencing at 5 months old and continued for 8 months. We had 2 control groups, young at 3 months and aged at 12 months old; these mice received no treatment. Brains were aldehyde-fixed and processed for immunohistochemistry with various glial and neuronal markers. We found a clear reduction in glial cell number, both astrocytes and microglia, in the striatum after PBM in aged mice. By contrast, the number of 2 types of striatal interneurons (parvalbumin+ and encephalopsin+), together with the density of striatal dopaminergic terminals (and their midbrain cell bodies), remained unchanged after such treatment. In summary, our results indicated that long-term PBM had beneficial effects on the aging striatum by reducing glial cell number; and furthermore, that this treatment did not have any deleterious effects on the neurons and terminations in this nucleus.

Treatment with 670 nm light up regulates cytochrome C oxidase expression and reduces inflammation in an age-related macular degeneration model.

Inflammation is an umbrella feature of ageing. It is present in the aged retina and many retinal diseases including age-related macular degeneration (AMD). In ageing and in AMD mitochondrial function declines. In normal ageing this can be manipulated by brief exposure to 670 nm light on the retina, which increases mitochondrial membrane potential and reduces inflammation. Here we ask if 670 nm exposure has the same ability in an aged mouse model of AMD, the complement factor H knockout (CFH(-/-)) where inflammation is a key feature. Further, we ask whether this occurs when 670 nm is delivered briefly in environmental lighting rather than directly focussed on the retina. Mice were exposed to 670 nm for 6 minutes twice a day for 14 days in the form of supplemented environmental light. Exposed animals had significant increase in cytochrome c oxidase (COX), which is a mitochondrial enzyme regulating oxidative phosphorylation.There was a significant reduction in complement component C3, an inflammatory marker in the outer retina. Vimetin and glial fibrillary acidic protein (GFAP) expression, which reflect retinal stress in Muller glia, were also significantly down regulated. There were also significant changes in outer retinal macrophage morphology. However, amyloid beta (Aß) load, which also increases with age in the outer retina and is pro-inflammatory, did not change. Hence, 670 nm is effective in reducing inflammation probably via COX activation in mice with a genotype similar to that in 50% of AMD patients even when brief exposures are delivered via environmental lighting. Further, inflammation can be reduced independent of Aß. The efficacy revealed here supports current early stage clinical trials of 670 nm in AMD patients.

Age-related retinal inflammation is reduced by 670 nm light via increased mitochondrial membrane potential.

The mitochondrial theory of aging argues that oxidative stress, caused by mitochondrial DNA mutations, is associated with decreased adenosine triphosphate (ATP) production leading to cellular degeneration. The rate of this degradation is linked to metabolic demand, with the outer retina having the greatest in the body, showing progressive inflammation, macrophage invasion, and cell loss, resulting in visual decline. Mitochondrial function shifts in vitro after 670-nm light exposure, reducing oxidative stress and increasing ATP production. In vivo, it ameliorates induced pathology. Here, we ask whether 670 nm light shifts mitochondrial function and reduces age-related retinal inflammation. Aged mice were exposed to only five 90-second exposures over 35 hours. This significantly increased mitochondrial membrane polarization and significantly reduced macrophage numbers and tumor necrosis factor (TNF)-alpha levels, a key proinflammatory cytokine. Three additional inflammatory markers were assessed; complement component 3d (C3d), a marker of chronic inflammation and calcitonin, and a systemic inflammatory biomarker were significantly reduced. Complement component 3b (C3b), a marker of acute inflammation, was not significantly altered. These results provide a simple route to combating inflammation in an aging population with declining visual function and may be applicable to clinical conditions where retinal inflammation is a key feature.