Aging plays ‘complex role’ in AMD pathogenesis
Oxidative stress, amyloid beta formation, circadian rhythm, metabolic aging and cellular senescence are among risk factors linked to age-related macular degeneration, according to a review published in Ageing Research Reviews.
“The most important structures in the retina are the neural retina and the [retinal pigment epithelium (RPE)], which can display different aging rates in different conditions,” Janusz Blasiak, from the department of molecular genetics at the University of Lodz in Poland, and colleagues wrote. “The functional and structural link between the neural retina and the RPE is expressed by the photoreceptors-RPE cells axis and may compensate for the different action of oxidative stress in the neural retina and the RPE, but several other aspects of pathogenesis, such as mitochondrial dysfunctions, changes in [Bruch’s membrane] and extracellular matrix as well as cellular senescence may differentially contribute to aging of these two structures.”
According to a review conducted by Blasiak and colleagues, oxidative stress may accelerate retinal aging, although too few studies have been performed to definitively conclude whether oxidative stress is a cause or consequence of AMD.
Another risk factor is formation of amyloid beta deposits, which have been linked to oxidative stress, decline in mitochondrial and lysosomal functions, inflammation and certain genotypes of the complement system. Evidence suggests these deposits may be a reliable marker of true retina aging.
Researchers also identified a link between AMD and cognitive decline, particularly in patients with dry AMD. However, data are inconsistent and require further research.
Disruption of circadian rhythm may also be linked to accelerated aging of neural retina and RPE, as well as cellular senescence, which is crucial for RPE cells and photoreceptor degeneration. However, cellular senescence may differently contribute to the aging process in these two types of cells.
Finally, metabolic aging may be associated with AMD, although it is currently difficult to define a group of metabolic pathways and metabolites that would contribute to AMD pathogenesis. However, most established AMD risk factors relate to cellular or organ metabolism.
“The complex role that aging may play in AMD pathogenesis is mainly due to complex interconnections with other AMD risk factors and its different rates in different retinal structures,” Blasiak and colleagues wrote. “Aging in AMD, similarly to general aging, still waits for a more precise definition and exploration, especially in the structures of the retina that are involved in AMD pathogenesis.”
Perspective
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Have you ever met a person and was shocked to learn that they were much older than you imagined? Some people look much younger than others the same age. These people are said to be “aging gracefully.” But the opposite situation also occurs — some people age much more quickly than most. People who “go downhill quickly” may have an identifiable reason for their rapid aging, such as a chronic health condition or poor lifestyle choices, but often it’s a mystery.
The authors of this paper distinguish between chronologic age (how old someone actually is) and biologic age (how quickly a person’s body has aged). This distinction is important in discussions of age-related disease because age itself is not a disease. Instead, age causes various metabolic functions to decline over time, and it’s the rate of this decline that determines when age-related diseases will appear.
A point of interest for the practicing optometrist is that the aging status of the retina appears to be a reliable marker for the biologic age of the body as a whole. Analysis of fundus images using artificial intelligence may someday yield a biologic age index that can predict the risk of various age-related diseases, such as Alzheimer’s disease. Maybe by then science will also give us a means to slow (or reverse) the aging process — but don’t hold your breath.
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