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Aging01:26

Aging

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Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
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Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
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At the molecular level, visual signals trigger transformations in photopigment molecules, resulting in changes in the photoreceptor cell's membrane potential. The photon's energy level is denoted by its wavelength, with each specific wavelength of visible light associated with a distinct color. The spectral range of visible light, classified as electromagnetic radiation, spans from 380 to 720 nm. Electromagnetic radiation wavelengths exceeding 720 nm fall under the infrared category,...
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Glaucoma is an eye condition characterized by increased intraocular pressure that damages the retina and optic nerve, leading to irreversible blindness if left untreated. The human eye has various components, including the cornea, iris, pupil, lens, and optic nerve. Aqueous humor is secreted by the epithelium of the ciliary body in the posterior chamber and flows through the trabecular meshwork and canal of Schlemm, maintaining normal intraocular pressure. The trabecular meshwork and the canal...
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Optical perception, or vision, is an extraordinary sense dependent on converting light signals received via the ocular organs. These organs, known as eyes, are securely positioned within the bony cavities of the skull, called orbits. The orbits serve a dual purpose: a protective shield for the ocular globes and a stable attachment point for the soft ocular tissues. The eye's external protective mechanisms include the eyelids, which are edged with lashes that act as a barrier against foreign...
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In open-angle glaucoma, the iridocorneal angle remains open, but the trabecular meshwork becomes stiff, slowing down the outflow of aqueous humor. This causes a buildup of aqueous humor in the anterior chamber, leading to a sudden increase in intraocular pressure. The treatment for open-angle glaucoma focuses on reducing the elevated intraocular pressure by either decreasing the secretion of aqueous humor or increasing its outflow.
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A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
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Proteostasis in aging-associated ocular disease.

Jasper Weinberg1, Mohita Gaur2, Anand Swaroop2

  • 1Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111, USA.

Molecular Aspects of Medicine
|December 2, 2022
PubMed
Summary

Maintaining protein homeostasis (proteostasis) is crucial for preventing age-related eye diseases like macular degeneration, cataracts, and glaucoma. Enhancing proteostatic machinery offers new therapeutic avenues for preserving vision in aging populations.

Keywords:
Age-related macular degenerationAgingAutophagyCataractDevelopmentDiabetesGlaucomaLensNutritionRetinaRetinopathyUbiquitin-proteasome system

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Area of Science:

  • Ophthalmology
  • Cell Biology
  • Gerontology

Background:

  • Vision impairment significantly impacts quality of life.
  • Proteostasis, the maintenance of cellular protein health, is vital for lifelong visual function, especially during aging.
  • Age-related eye diseases like AMD, cataracts, and glaucoma are linked to proteostatic decline.

Purpose of the Study:

  • To review the fundamental aspects of proteostasis.
  • To discuss the role of proteostasis in major age-related eye diseases.
  • To identify opportunities for therapeutic interventions targeting proteostatic pathways in the aging eye.

Main Methods:

  • Review of basic proteostasis mechanisms (synthesis, folding, degradation).
  • Analysis of proteostatic challenges in aging ocular tissues (retina, lens, trabecular meshwork).
  • Examination of the ubiquitin-proteasome and autophagy-lysosome systems in age-related eye disease.

Main Results:

  • Aging and chronic stress increase proteostatic burden.
  • Degradation pathways (ubiquitin-proteasome, autophagy-lysosome) become less efficient with age.
  • This leads to the accumulation of damaged proteins, contributing to ocular pathologies.

Conclusions:

  • A "double jeopardy" of increased proteostatic load and decreased degradation efficiency accelerates protein accumulation in aging eyes.
  • Balancing protein synthesis and degradation is challenging but critical.
  • Harnessing proteostasis presents a promising strategy for developing interventions against age-related eye diseases.