Aging Alters Circadian Rhythms in the Mouse Eye

“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).”

“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).”

“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).”

“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.”

“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).”

“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).”

“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).”

“In this context, it is important to note that these effects are observed in the peripheral oscillators and not in the SCN, in which aging causes a phase delay (Asai et al., 2001; Sellix et al., 2012; Davidson et al., 2008; Nakamura et al., 2015; Yamazaki et al., 2002).”

“, 2012), photoreceptor viability is also reduced (Gresh et al., 2003; Baba et al., 2009; Gianesini et al., 2016), and dysfunction in the circadian clock leads to photoreceptor loss (Baba et al.”

“, 2012), photoreceptor viability is also reduced (Gresh et al., 2003; Baba et al., 2009; Gianesini et al., 2016), and dysfunction in the circadian clock leads to photoreceptor loss (Baba et al.”

“Previous studies have reported age-related loss of corneal endothelial cells (Bourne and McLaren, 2004; Gipsen, 2013), and we have previously shown that in the cornea the PER2::LUC bioluminescence signal is mostly emitted by the corneal epithelium and endothelium (Baba et al.”

“In this context, it is important to note that these effects are observed in the peripheral oscillators and not in the SCN, in which aging causes a phase delay (Asai et al., 2001; Sellix et al., 2012; Davidson et al., 2008; Nakamura et al., 2015; Yamazaki et al., 2002).”

“However, progressive desynchronization of oscillators among SCN neurons, not a reduction in clock function, is thought to be the underlying cause of age-dependent reductions in amplitude (Nakamura et al., 2015).”

“However, the Bmal1::LUC circadian rhythm of fibroblasts obtained from young individuals was shorter and phase-shifted when cells were treated with serum obtained from old individuals (Pagani et al., 2011).”

“Previous studies have shown that aging affects the circadian rhythms in locomotor activity, suprachiasmatic nucleus of the hypothalamus (SCN), and peripheral organs (Aujard et al., 2001; Yamazaki et al., 2002; Davidson et al., 2008; Sellix et al., 2012; Nakamura et al., 2015; Tahara et al., 2017).”

“Because culture preparation of ocular tissues can be affected by the time of the day at which the cultures are prepared (Evans et al., 2015), all of the cultures were prepared under fluorescent light between ZT 8 and 10.”

“Previous studies have shown that aging affects the circadian rhythms in locomotor activity, suprachiasmatic nucleus of the hypothalamus (SCN), and peripheral organs (Aujard et al., 2001; Yamazaki et al., 2002; Davidson et al., 2008; Sellix et al., 2012; Nakamura et al., 2015; Tahara et al., 2017).”

“Previous studies have reported age-related loss of corneal endothelial cells (Bourne and McLaren, 2004; Gipsen, 2013), and we have previously shown that in the cornea the PER2::LUC bioluminescence signal is mostly emitted by the corneal epithelium and endothelium (Baba et al., 2015).”

“, 2010), and Clock/Npas2 KO mice showed a significant reduction in the thickness of the photoreceptor layer (Baba et al., 2018).”

“In the mouse, visual processing steadily decreases during aging (Gresh et al., 2003; Baba et al., 2012), photoreceptor viability is also reduced (Gresh et al., 2003; Baba et al., 2009; Gianesini et al., 2016), and dysfunction in the circadian clock leads to photoreceptor loss (Baba et al., 2018).”

“, 2012), which was used to determine the dominant periodicity in the data fit by the cosine function with the highest amplitude (Herzog et al., 2014).”

“In the mouse, visual processing steadily decreases during aging (Gresh et al., 2003; Baba et al., 2012), photoreceptor viability is also reduced (Gresh et al., 2003; Baba et al., 2009; Gianesini et al., 2016), and dysfunction in the circadian clock leads to photoreceptor loss (Baba et al., 2018).”

“The eye contains a circadian system and aging affects the circadian rhythm of the retina (Baba and Tosini, 2018).”