Normal ageing is associated with a decline in the quality of mitochondria and its
function. Mitochondrial dysfunction is affiliated with reduced production of ATP, a
characteristic feature of ageing and disease. Therefore, mitochondria are key targets of
therapeutic agents. Aged mitochondrial function can be improved optically by longwavelength light (650-900nm) exposure, resulting in increased ATP production and
reduced ROS. These changes translate into improved functionality from flies to
humans.
This thesis aims to assess the contribution of mitochondrial dysfunction in ageing,
especially in a metabolically demanding environment such as the retina; and investigate
the effects of 670nm light exposure in improving aged function. This will be achieved
using three animal models flies, mice, and primates, before translating findings to
humans.
Flies revealed a decline of mitochondrial function with age and shifts of these functions
across the day. The functional shifts revealed optimal timings for 670nm exposure in
improving mitochondrial function. The ageing mouse retina showed changes in
mitochondrial dynamics that altered with 670nm exposure, especially in the
photoreceptor layer. Mitochondrial biogenesis declined with age, and the CFH-/- mouse
revealed further disruptions of this process. The immune system, by assessing cytokine
patterns, demonstrated a decline with age which altered following 670nm exposure.
The ageing primate retina revealed a decline in mitochondrial membrane potentials and
ultrastructure. Cone cells are characterised by high mitochondrial density, they
demonstrated altered patterns of mitochondrial dynamics with age.
Translating evidence from animal models to humans revealed a decline in
electroretinograms and colour vision with age. Older subjects showed improvement to
visual function following 2 weeks of 670nm exposure. Investigations of single exposures
of red light demonstrated improved colour vision only when light was delivered in the
morning, similar to findings in flies.
This thesis was able to demonstrate the universal nature of mitochondrial ageing across
species and how this can be ameliorated with exposure to long-wavelength light.