Harpreet Shinhmar, MSc, Manjot Grewal, BSc, Sobha Sivaprasad, MBBS, PhD, Chris Hogg, Victor Chong, MBBS, PhD, Magella Neveu, PhD, Glen Jeffery, DPhil, Optically Improved Mitochondrial Function Redeems Aged Human Visual Decline, The Journals of Gerontology: Series A, Volume 75, Issue 9, September 2020, Pages e49–e52, https://doi.org/10.1093/gerona/glaa155
The age spectrum of human populations is shifting toward the older with larger proportions suffering physical decline. Mitochondria influence the pace of aging as the energy they provide for cellular function in the form of adenosine triphosphate (ATP) declines with age. Mitochondrial density is greatest in photoreceptors, particularly cones that have high energy demands and mediate color vision. Hence, the retina ages faster than other organs, with a 70% ATP reduction over life and a significant decline in photoreceptor function. Mitochondria have specific light absorbance characteristics influencing their performance. Longer wavelengths spanning 650–>1,000 nm improve mitochondrial complex activity, membrane potential, and ATP production. Here, we use 670-nm light to improve photoreceptor performance and measure this psychophysically in those aged 28–72 years. Rod and cone performance declined significantly after approximately 40 years of age. 670-nm light had no impact in younger individuals, but in those around 40 years and older, significant improvements were obtained in color contrast sensitivity for the blue visual axis (tritan) known to display mitochondrial vulnerability. The red visual axis (protan) improved but not significantly. Rod thresholds also improved significantly in those >40 years. Using specific wavelengths to enhance mitochondrial performance will be significant in moderating the aging process in this metabolically demanding tissue.
This pilot study has limitations due to its sample size, but the results reveal significant improvement in both rod and cone function in an aged cohort but not in younger individuals. This difference is presumably because age-related mitochondrial decline has not yet affected the younger individuals. Widespread positive results using long-wavelength light in aging and disease in animals have provided an impetus for their clinical application in full-scale clinical trials for diabetic retinopathy (NCT03866473) and age related macular degeneration (NCT02725762, 03878420). However, a recently published study on AMD patients has failed to show any improvement in retinal function in this disease (25). Consequently, there is much that we still need to understand regarding the advantages and limits of this therapeutic route.