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Repeated stress accelerates eye aging

Summary: Stress such as elevated intraocular pressure in the eye causes transcriptional and epigenetic changes in retinal tissue similar to natural aging.

Source: UC Irvine

New research from the University of California, Irvine suggests that aging is an important component of retinal ganglion cell death in glaucoma, and that new pathways can be targeted when designing new treatments for patients with glaucoma. glaucoma.

The study was published today in aging cell. Along with her colleagues, Dorota Skowronska-Krawczyk, Ph.D., assistant professor in the Departments of Physiology and Biophysics and Ophthalmology and faculty at the Center for Translational Research in Vision at the UCI School of Medicine, describes the transcriptional and epigenetic changes that occur in retinal aging.

The team shows how stress, such as elevated intraocular pressure (IOP) in the eye, causes epigenetic and transcriptional changes in retinal tissue similar to natural aging. And how, in young retinal tissue, repetitive stress induces characteristics of accelerated aging, including accelerated epigenetic age.

Aging is a universal process that affects every cell in an organism. At eye level, it is a major risk factor for a group of neuropathies called glaucoma. Due to increasing aging populations around the world, current estimates show that the number of people with glaucoma (aged 40-80) will increase to over 110 million by 2040.

“Our work emphasizes the importance of early diagnosis and prevention as well as age-specific management of age-related diseases, including glaucoma,” Skowronska-Krawczyk said.

“The epigenetic changes we observed suggest that changes at the chromatin level are acquired cumulatively, following multiple instances of stress. This gives us a window of opportunity for the prevention of vision loss, if and when the disease is recognized early.

In humans, IOP has a circadian rhythm. In healthy individuals, it generally hovers between 12 and 21 mmHg and tends to be highest in about two-thirds of individuals during the night period.

Due to fluctuations in IOP, a single IOP measurement is often insufficient to characterize true pathology and risk of disease progression in patients with glaucoma.

Long-term IOP fluctuation has been reported to be a strong predictor of glaucoma progression. This new study suggests that the cumulative impact of IOP fluctuations is directly responsible for tissue aging.

When the UCI-led team investigated the optic nerve head of treated eyes with mild pressure elevation, they noted that in the young optic nerve head there was no evidence of loss of pressure. axons. However, in the optic nerves of aged animals, a significant sectoral loss of axons was observed similar to the phenotype commonly observed in patients with glaucoma. Credit: UCI School of Medicine

“Our work shows that even moderate hydrostatic elevation of IOP leads to retinal ganglion cell loss and corresponding visual defects when performed on aged animals,” Skowronska-Krawczyk said.

“We continue to work to understand the mechanism of cumulative changes in aging in order to find potential targets for therapeutics. We are also testing different approaches to prevent the accelerated aging process resulting from stress.

Researchers now have a new tool to estimate the impact of stress and treatments on the aging state of retinal tissue, which made these new findings possible. In collaboration with the Clock Foundation and Steve Horvath, Ph.D., of Altos Labs, who pioneered the development of epigenetic clocks capable of measuring age based on methylation changes in tissue DNA, it was possible for the researchers to show that repetitive clocks, a slight elevation in IOP can accelerate the epigenetic age of tissues.

“In addition to measuring vision decline and some structural changes due to stress and potential treatment, we can now measure the epigenetic age of retinal tissue and use it to find the optimal strategy to prevent vision loss with the aging,” Skowronska-Krawczyk said.

About this visual neuroscience research news

Author: Press office
Source: UC Irvine
Contact: Press Office – UC Irvine
Image: Image is credited to UC Irvine

Original research: Free access.
Stress-induced aging in mouse eye” by Qianlan Xu et al. aging cell


Summary

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Stress-induced aging in mouse eye

Aging, a universal process that affects every cell in an organism, is a major risk factor for a group of neuropathies called glaucoma, where elevated intraocular pressure is one of the known stresses affecting tissues.

Our understanding of the molecular impact of aging on the stress response in the retina is very limited; therefore, we developed a new mouse model to address this issue experimentally.

Here we show that sensitivity to the stress response increases with age and is primed at the chromatin level.

We demonstrate that ocular hypertension activates a stress response similar to natural aging and involves the activation of inflammation and senescence.

We show that multiple instances of pressure elevation cause aging of the young retina, measured at the level of transcription and DNA methylation, and are accompanied by local histone modification changes.

Our data show that repeated stress accelerates the onset of aging features in tissues and suggests chromatin changes as key molecular components of aging.

Finally, our work further emphasizes the importance of early diagnosis and prevention as well as age-specific management of age-related diseases, including glaucoma.

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