Why does the amplitude of the circadian rhythm decrease with age?

Age-Related Decline in Circadian Rhythm Amplitude: Mechanisms and Implications

The amplitude of circadian rhythms decreases with age primarily due to degenerative changes in the suprachiasmatic nucleus (SCN), reduced light sensitivity, and altered interactions between circadian and homeostatic processes that regulate sleep-wake cycles. 1

Neurobiological Mechanisms

• Age-related changes in the SCN, the central circadian pacemaker in the hypothalamus, contribute significantly to decreased rhythm amplitude, with studies showing loss of neurons and deleterious changes within the SCN in older adults 1
• Research using PER2::LUC protein expression monitoring reveals that aging affects the circadian system downstream from the core molecular clock, impairing the interaction between the molecular clock and cellular components 2
• The SCN circadian ensemble becomes degraded with age, with individual SCN cells showing longer circadian periods and becoming rapidly desynchronized, leading to reduced robustness of the central pacemaker 3

Light Sensitivity and Environmental Factors

• Aging is associated with decreased light sensitivity due to anatomical changes such as reduced lens transparency and smaller pupil diameter, limiting the amount of light reaching the retina and subsequently the SCN 1
• Photosensitive retinal ganglion cells (pRGCs), which provide the primary conduit for light information to reach the SCN, may undergo age-related changes affecting their function 1
• Paradoxically, some studies show that healthy older adults may actually be exposed to higher levels of light throughout their waking day compared to younger people, suggesting that light exposure patterns rather than total exposure may be more relevant 4

Circadian-Homeostatic Interaction

• The interaction between circadian timing and homeostatic sleep drive changes with age, with evidence showing a reduction in both the homeostatic drive for sleep and the strength of the circadian signal promoting sleep 1
• This altered interaction particularly affects early morning sleep maintenance in older individuals, contributing to common complaints of early morning awakening 1
• The phase relationship (phase angle) between wake time and circadian markers like melatonin secretion or core body temperature nadir shortens with age, affecting sleep quality 4

Hormonal and Physiological Changes

• Age-related dampening of 24-hour endocrine rhythms, including cortisol and growth hormone, reflects changes in both circadian rhythmicity and sleep-wake homeostasis 5
• Melatonin rhythm shows lower amplitude in older subjects compared to younger subjects, which may contribute to sleep disturbances and circadian rhythm disruptions 6
• The blunting of temperature nadir during sleep in older adults reflects disruption of normal circadian temperature regulation, which can affect sleep quality 7

Clinical Manifestations

• Advanced sleep phase disorder (ASPD) is common in older adults, characterized by earlier sleep onset and wake times, which may reflect the age-related phase advance of the circadian system 1
• Irregular sleep-wake disorder (ISWD) can develop in older adults, particularly those with dementia, characterized by fragmented sleep distributed throughout the 24-hour day 1
• These disorders manifest as habitually earlier bedtimes and wake times, inability to maintain sleep through the night, undesired early morning awakening, and frequent daytime sleepiness 1

Therapeutic Implications

• Bright light therapy can help consolidate circadian rhythms in older adults, with exposure of 3,000 to 5,000 lux for 2 hours in the morning shown to decrease daytime napping and increase nighttime sleep 1
• Structured physical and social activity can provide temporal cues to increase the regularity of the sleep-wake schedule in older adults 1
• A multidimensional approach including increased sunlight exposure during the day, decreased time in bed during daytime, and improved sleep environment may be particularly effective in managing age-related circadian rhythm disorders 1

Research Considerations

• The full impact of aging on molecular rhythms in the SCN may be masked by daily exposure to light-dark cycles, with the effects becoming more apparent under constant dark conditions 3
• Phase-shifting responses to moderate or high-intensity light may not be significantly affected by age, suggesting that the circadian system remains responsive to light stimuli despite age-related changes 6
• The decreased amplitude of circadian rhythms with age may increase vulnerability to environmental challenges, partly explaining age-related sleep and circadian disturbances 3