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Aging Alters Circadian Rhythms in the Mouse Eye
Open accessAbstract
The eye contains a circadian system that acts independently from the master circadian clock located in the brain. This circadian system regulates important physiological functions within the eye. Emerging experimental evidence also indicates that disruption of the ocular circadian clock, or its outputs, negatively affects the overall health of the eye. Although previous studies have investigated the effect of aging on the regulation of circadian rhythms, no study has investigated the effects of aging on the circadian rhythm in the ocular system. The aim of the present study was to investigate how aging affects the circadian rhythm of PER2::LUC bioluminescence in the retina, retinal pigment epithelium (RPE), and cornea. Our data suggest that among the 3 different ocular tissues investigated, the retina appears to be the most affected by aging whereas the RPE and cornea are less affected by aging. Our data, along with studies of other organs and tissues, suggest that reduction in the amplitude of rhythms is probably the most severe effect of aging on the circadian clock.
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“A recent study further suggests that the aging of retinal tissue most severely effects the reduction in amplitude of rhythm of the circadian clock 51.”
From The inner clock-Blue light sets the human rhythm (2019) · cites this paper as [51]
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“Our data agree with previous studies which reported that amplitudes of circadian rhythms in the SCN and other tissues decline during aging (Nakamura et al., 2011; Nakamura et al., 2015; Aujard et al., 2001).”
Effects of aging on central and peripheral mammalian clocks
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“In contrast, aging did not affect the phase and period of PER2::LUC rhythm in the mouse cornea, consistent with data from rat corneas (Yamazaki et al., 2002).”
InfluentialCircadian organization of the mammalian retina: From gene regulation to physiology and diseases
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“This circadian system regulates important functions such as visual processing, susceptibility to light-induced photoreceptor damage, neurotransmitter synthesis and release, disk shedding and phagocytosis, corneal thickness, and intraocular pressure (see McMahon et al., 2014, for a recent review).”
InfluentialSelf-citationDubrovsky, Y. V., Samsa, W. E., & Kondratov, R. V. (2010) · Aging · doi:10.18632/aging.100241 · Cited by 193 · cited 1×
“Clock mutant mice developed cataracts during aging (Dubrovsky et al., 2010), and Clock/Npas2 KO mice showed a significant reduction in the thickness of the photoreceptor layer (Baba et al.”
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“A decline in amplitude of the bioluminescence rhythm of xiphoid cartilage explanted from 20- to 24-month-old PER2::LUC mice and intervertebral disk from 12-month-old PER2::LUC mice also showed a damped circadian amplitude (Gossan et al., 2013; Dudek et al., 2017).”
Dudek, M., Yang, N., Ruckshanthi, J. P. D., Williams, J. L., Borysiewicz, E., Wang, P., Adamson, A. D., Li, J., Bateman, J. F., White, M., et al. (2016) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2016-209428 · Cited by 167 · cited 1×
“A decline in amplitude of the bioluminescence rhythm of xiphoid cartilage explanted from 20- to 24-month-old PER2::LUC mice and intervertebral disk from 12-month-old PER2::LUC mice also showed a damped circadian amplitude (Gossan et al., 2013; Dudek et al., 2017).”
Sellix, M. T., Evans, J. A., Leise, T., Castañón‐Cervantes, O., Hill, D. D., Delisser, P., Block, G. D., Menaker, M., & Davidson, A. J. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3559-12.2012 · Cited by 153 · cited 4×
“While this period-phase relationship would not be predicted from classic circadian entrainment theory, it is consistent with previous investigations in the mouse (Nakamura et al., 2015; Yamazaki et al., 2002; Sellix et al., 2012).”
Influential
Research works printed but not linked: 1
- Baba K, 2010, Mol Vis, 16, 2605
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“The eye contains a circadian system and aging affects the circadian rhythm of the retina (Baba and Tosini, 2018).”
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Rods contribute to the light-induced phase shift of the retinal clock in mammals
Calligaro, H., Coutanson, C., Najjar, R. P., Mazzaro, N., Cooper, H. M., Haddjeri, N., Felder‐Schmittbuhl, M., & Dkhissi‐Benyahya, O. (2019) · PLoS Biology · doi:10.1371/journal.pbio.2006211 · Cited by 45
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“The circadian clock is an intrinsic timekeeping system that regulates multiple vital physiological and biochemical processes, including cell proliferation and senescence (18,19).”
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“Finally, it is worth mentioning that the age of the mice and the time of the day at which the tissue is explanted and prepared for the culture preparation may affect the circadian parameters, and thus it should be carefully considered [7,70].”
BackgroundSelf-citationMilićević, N., Mazzaro, N., de Bruin, I., Wils, E., ten Brink, J. B., ten Asbroek, A. L. M. A., Mendoza, J., Bergen, A. A. B., & Felder‐Schmittbuhl, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-48203-3 · Cited by 28
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Self-citationThe circadian clock regulates RPE-mediated lactate transport via SLC16A1 (MCT1)
Milićević, N., ten Brink, J. B., ten Asbroek, A. L. M. A., Bergen, A. A. B., & Felder‐Schmittbuhl, M. (2019) · Experimental Eye Research · doi:10.1016/j.exer.2019.107861 · Cited by 18
“Considering that the RPE harbors a circadian oscillator (Baba et al., 2017; 82 Baba et al., 2010; Baba and Tosini, 2018), we hypothesize that the RPE circadian clock meets the daily 83 metabolic needs of photoreceptors via rhythmic expression of glucose and monocarboxylate 84 transporters.”
BackgroundRNA Splicing Factor Mutations That Cause Retinitis Pigmentosa Result in Circadian Dysregulation
Shakhmantsir, I., Dooley, S. J., Kishore, S., Chen, D., Pierce, E. A., Bennett, J., & Sehgal, A. (2019) · Journal of Biological Rhythms · doi:10.1177/0748730419887876 · Cited by 11
“Aging causes dampening of circadian cycles in the eye, particularly in the retina (Baba and Tosini, 2018).”
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“There is evidence that the proper timekeeping is responsible for healthy aging and is associated with longevity [9,11], the aging itself may affect circadian rhythmicity [11-13].”
BackgroundImportance of Circadian Rhythms in the Ocular Surface
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“Ocular tissues are proven to contain the core molecular circadian system and exhibit integrated rhythms of circadian activities [5–7].”
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“In addition to lower PER2 bioluminescence amplitudes, aged retinas and RPE had significantly different acrophases, suggesting that these clocks decouple during aging (Baba and Tosini 2018).”
BackgroundCircadian rhythms in ophthalmic diseases
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Metadata
- Authors
- Baba, K., & Tosini, G.
- Affiliations
- Morehouse School of Medicine (US)
- Corresponding author
- Tosini, Gianluca
- Venue
- Journal of Biological Rhythms
- Publisher
- SAGE Publications
- Published
- 2018-06-25
- Volume
- 33
- Issue
- 4
- Pages
- 441-445
- ISSN
- 0748-7304 (ISSN-L)
- 1552-4531
- PMC
- PMC6398161
- OpenAlex
- W2811137840
- Cited by
- 35
- References
- 28
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 10 · 2018: 2
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Biological Rhythms (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS083932)
- National Eye Institute (EY022216, EY026291)
- National Institute of General Medical Sciences (GM116760)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- aging, circadian rhythm, retina, retinal pigment epithelium, cornea, ocular aging
- MeSH terms
- Aging, Animals, Circadian Rhythm, Cornea, Luminescent Measurements, Retina, Mice, Retinal Pigment Epithelium, Period Circadian Proteins, Circadian Clocks
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