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The Aging Stress Response and Its Implication for AMD Pathogenesis

1
Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
2
Department of Orthodontics, Medical University of Lodz, 92-216 Lodz, Poland
3
Department of Gynaecology and Obstetrics, Medical University of Lodz, 93-338 Lodz, Poland
4
Department of Pediatric Dentistry, Medical University of Lodz, 92-216 Lodz, Poland
5
Department of Ophthalmology, University of Eastern Finland, 70211 Kuopio, Finland
6
Department of Ophthalmology, Kuopio University Hospital, 70211 Kuopio, Finland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8840; https://doi.org/10.3390/ijms21228840
Received: 13 October 2020 / Revised: 12 November 2020 / Accepted: 20 November 2020 / Published: 22 November 2020
(This article belongs to the Special Issue Molecular Research of Aging Stress Response)
Aging induces several stress response pathways to counterbalance detrimental changes associated with this process. These pathways include nutrient signaling, proteostasis, mitochondrial quality control and DNA damage response. At the cellular level, these pathways are controlled by evolutionarily conserved signaling molecules, such as 5’AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), insulin/insulin-like growth factor 1 (IGF-1) and sirtuins, including SIRT1. Peroxisome proliferation-activated receptor coactivator 1 alpha (PGC-1α), encoded by the PPARGC1A gene, playing an important role in antioxidant defense and mitochondrial biogenesis, may interact with these molecules influencing lifespan and general fitness. Perturbation in the aging stress response may lead to aging-related disorders, including age-related macular degeneration (AMD), the main reason for vision loss in the elderly. This is supported by studies showing an important role of disturbances in mitochondrial metabolism, DDR and autophagy in AMD pathogenesis. In addition, disturbed expression of PGC-1α was shown to associate with AMD. Therefore, the aging stress response may be critical for AMD pathogenesis, and further studies are needed to precisely determine mechanisms underlying its role in AMD. These studies can include research on retinal cells produced from pluripotent stem cells obtained from AMD donors with the mutations, either native or engineered, in the critical genes for the aging stress response, including AMPK, IGF1, MTOR, SIRT1 and PPARGC1A. View Full-Text
Keywords: the aging stress response; aging; age-related macular degeneration; AMD; insulin/IGF-1; SIRT1; PGC-1α; autophagy; DNA damage response; mitochondrial quality control the aging stress response; aging; age-related macular degeneration; AMD; insulin/IGF-1; SIRT1; PGC-1α; autophagy; DNA damage response; mitochondrial quality control
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MDPI and ACS Style

Blasiak, J.; Pawlowska, E.; Sobczuk, A.; Szczepanska, J.; Kaarniranta, K. The Aging Stress Response and Its Implication for AMD Pathogenesis. Int. J. Mol. Sci. 2020, 21, 8840. https://doi.org/10.3390/ijms21228840

AMA Style

Blasiak J, Pawlowska E, Sobczuk A, Szczepanska J, Kaarniranta K. The Aging Stress Response and Its Implication for AMD Pathogenesis. International Journal of Molecular Sciences. 2020; 21(22):8840. https://doi.org/10.3390/ijms21228840

Chicago/Turabian Style

Blasiak, Janusz; Pawlowska, Elzbieta; Sobczuk, Anna; Szczepanska, Joanna; Kaarniranta, Kai. 2020. "The Aging Stress Response and Its Implication for AMD Pathogenesis" Int. J. Mol. Sci. 21, no. 22: 8840. https://doi.org/10.3390/ijms21228840

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