Aging is a complex process for which distinct molecular aspects contribute to age-related tissue dysfunction. Systematic analysis of epigenomic and transcriptomic changes across mouse tissues during aging identified several recurring processes including interferon alpha response, IL6-JAK-STAT3 signaling, complement, and other components of innate immune response being gradually upregulated with age.
Glaucoma, an age-related eye disease, is characterized by progressive neurodegeneration of the optic nerve that if untreated leads to morphological changes, functional decline, and eventual blindness. Age is the most consistent risk factor for glaucoma. By contrast, other risk factors, including elevated intraocular pressure (IOP), family history, and high myopia, exhibit more variability.
Pathophysiological stress related to elevated IOP induces a broad spectrum of changes in the connective tissues and blood vessels that are central to the function of the retina. They also induce molecular changes in retinal cells, including retinal ganglion cells (RGCs).
New research suggests aging is an important component of retinal ganglion cell death in glaucoma
The team shows how stress, such as intraocular pressure (IOP) elevation in the eye, causes retinal tissue to undergo epigenetic and transcriptional changes similar to natural aging. And, how in young retinal tissue, repetitive stress induces features of accelerated aging including the accelerated epigenetic age.
Researchers now have a new tool to estimate the impact of stress and treatment on the aging status of retinal tissue, which has made these new discoveries possible. In collaboration with the Clock Foundation and Steve Horvath, PhD, from Altos Labs, who pioneered the development of epigenetic clocks that can measure age based on methylation changes in the DNA of tissues, it was possible for researchers to show that repetitive, mild IOP elevation can accelerate epigenetic age of the tissues.
In addition to measuring vision decline and some structural changes due to stress and potential treatment, they can now measure the epigenetic age of retinal tissue and use it to find the optimal strategy to prevent vision loss in aging,
Qianlan Xu, Cezary Rydz, Viet Anh Nguyen Huu, Lorena Rocha, Claudia Palomino La Torre, Irene Lee, William Cho, Mary Jabari, John Donello, David C. Lyon, Robert T. Brooke, Steve Horvath, Robert N. Weinreb, Won‐Kyu Ju, Andrzej Foik, Dorota Skowronska‐Krawczyk. Stress induced aging in mouse eye. Aging Cell, 2022; DOI: 10.1111/acel.13737
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