Table of contents

How Sleep Impacts Aging

Sleep is incredibly important for the human body as a whole as well as on the cellular level. What causes alterations in the quantity and quality of sleep and what are the consequences of these changes are quite important questions. What changes exacerbate aging and a more dysfunctional physiology and what changes are caused by aging that are detrimental to your health as well. We will cover the characterization of related changes in sleep structure on both the macro and micro scale and cover the differences between men and women when it comes to sleep and age.

sleep

13 mins

By: Daniel Tawfik

How Sleep Impacts Aging

Mander, Bryce A et al. “Sleep and Human Aging.” Neuron vol. 94,1 (2017): 19-36. doi:10.1016/j.neuron.2017.02.004

Macro Sleep Changes:

First let's cover alterations in sleep that occur in your body as a whole or macro sleep changes. When you age your quality and quantity of sleep changes, you yourself can attest to this. Once you're into your 50’s your sleep architecture goes through some radical changes, as shown in figure 1. Now these changes are not universal and each individual will present different changes in their sleep architecture, if any at all.

Macro Sleep Changes:

Advanced sleep timing - Sleep occurs between 6 p.m. and 9 p.m. with waking between the hours of 2 a.m. and 5 a.m.
Longer sleep-onset latency - The longer it takes for sleep to occur, the longer it will take to reach the first REM sleep stage.
Shorter overall sleep duration - The sleep that does occur, happens in shorter than usual time spans.
Increased sleep fragmentation - Sleep fragmentation is the total number of awakenings and transition to stage 1 sleep divided by the total sleep time, or those brief moments of wakefulness that occur when you're sleeping.
More fragile sleep - Sleep that is easily disrupted or waking up because of every little bump in the night.
Reduced amount of deeper NREM sleep - The reduction of sleep in which your body begins to relax.
Increased time spent in lighter NREM Stages 1 and 2 - While sleeping you will spend more time in NREM s\Stages 1 and 2
Shorter and fewer NREM-REM sleep cycles - While sleeping, you will only experience a few cycles between non-REM and REM, compared to the standard amount for a healthy human body.
Increased time spent awake throughout the night - Sleep that is constantly disrupted by the classic tossing and turning.

Macro Sleep Changes:

Age-related reduction of time in REM sleep might pose a more distant threat for those in their 80’s due to only emerging then as a stand-alone issue but is often more so linked to changes within your NREM sleep cycles or as symptoms of degenerative dementia. Ohayon et al., 2004, Van Cauter et al., 2000, Brayet et al., 2015, Hita-Yañez et al., 2012, Petit et al., 2004,

Additionally, the increase in naps during the day also increases as you age, with 10% of adults aged 55-64, and 25% of adults aged 75-84, reporting daytime naps. With roughly half of these two groups’ naps being unplanned, which is consistent with the claim that 1 in 4 of older adults report that daytime sleepiness impairs their daytime plans on a regular basis. These daytime abnormalities may reflect the sleep issues that affect older adults were discussed earlier. Foley et al., 2007

Excessive daytime sleepiness and naps are not universal for old age, with some adults reporting diminished or less daytime sleepiness as well. Dijk et al., 2010 The one factor that appears to control whether or not an adult will be prone to daytime sleepiness or naps is the presence of multiple conditions such as chronic pain, depression, sleep disorders, and frequent urination during the night. Foley et al., 2007, Vitiello, 2009. The propensity of daytime sleepiness can be higher in an otherwise healthy older adult than a younger adult in the evening despite the circadian alerting signal being at its peak in young adults. Münch et al., 2005 Thus, the discrepancies between daytime sleepiness in older adults appears to partially depend on the time of day and/or circadian preference of the individual adults being compared. This becomes further relevant given the advancement in circadian preference in older adults, wherein older adults shift to early bedtimes and early wake times. Monk, 2005

Micro Sleep Changes:

In addition to larger macros sleep changes, there are just as significant changes within the signature electrical oscillations of sleep. Signature electrical oscillations, which are measured with electroencephalography (EEG), are most prominent within NREM sleep and two of its fellow oscillations, slow waves and sleep spindles, which are the pattern of brain waves that occur during NREM sleep. (fig 1).

One method of quantifying slow waves is through the measurement of spectral power in the 0.5-4.5 Hz range during NREM sleep or slow wave sleep, also known as slow wave activity (SWA). While reductions in SWA are observed in middle-aged adults and becomes especially pervasive in older adults.Dijk et al., 1989, Landolt and Borbély, 2001, Landolt et al., 1996, Mander et al., 2013.

It's important to note that age-related decreases in SWA are not evenly distributed with respect to head topography or sleep cycles throughout the night. Instead, maximal age-related decrements in absolute SWA are observed over the prefrontal cortex derivations and in the first NREM sleep cycles, with 75%-80% reductions on average relative to you adults (Fig 1). Dijk et al., 1989, Landolt and Borbély, 2001, Landolt et al., 1996, Mander et al., 2013

SWA is tightly bound to the homeostatic drive to sleep following continued wakefulness, that is the longer you're awake, the greater the pressure and desire to sleep is, additionally the amount of SWA will increase proportional to the time spent awake. Borbély, 1982. For young adults, SWA is highest within the first NREM cycle of the night and then SWA decreases as the night progresses in successive NREM sleep cycles. This decrease in SWA reflects the homeostatic dissipation of sleep pressure as you sleep through the night; that is, the more tired you are, the more slow wave activity there will be (Fig 2). Landolt and Borbély, 2001, Landolt et al., 1996

The process of homeostatic sleep regulation, including SWA, is also changed as a function of aging. The exponential slope of SWA dissipation through the night is less in older adults when compared to those younger (Fig 2A). Landolt and Borbély, 2001 Landolt et al., 1996 Additionally, homeostatic increases in slow wave sleep time and SWA in response to staying awake to the point of sleep deprivation or selective slow wave sleep suppression are blunted within older adults compared to younger adults (Fig 2B). Landolt and Borbély, 2001, Munch et al., 2004. This finding has been interpreted as an impairment of the homeostatic regulation of SWA in older adults. This has been interpreted as an impairment in SWA homeostatic regulation in older adults, with the changes in these homeostatic SWA features in aging are also observed in the prefrontal cortex. Dijk et al., 2010, Munch et al., 2004.

Underlying the changes in SWA is the expression of two NREM slow wave features, the amplitude of slow waves and the density of slow waves, being significantly reduced within middle-aged adults. This reduction is further exacerbated as you age, with further reductions in amplitude and density.Carrier et al., 2011, Dubé et al., 2015. Note that these age-related fluctuations in amplitude and density are not uniform across the brain and that these age-related differences are more prevalent during the 1st and 2nd stages of NREM sleep cycles. Additionally the slope of the slow waves becomes increasingly shallower as you age. These changes suggest that aging may diminish and degrade the synchronized neuronal en masse firing that creates the sleep oscillations, via the disruption of the polarization needed to shape the slow waves. Beenhakker and Huguenard, 2009.

Another drastic change is the reduction of slow wave frequency to roughly 0.1 Hz in older adults. This reduction in frequency can also be observed throughout the brain as opposed to the area specific changes of amplitude and density. Surprisingly the reduction of slow wave frequency is not found within older adults with Beta-amyloid (Aβ) burden and adults with poor memory retention. This link possibly give credence to using slow wave frequency as a new sleep biomarker in distinguishing normal aging versus abnormal aging within the context of Alzheimer's disease pathophysiology. Mander et al., 2016a, Carrier et al., 2011.

The sleep spindle, another definer of NREM sleep oscillation, goes through its own changes during your later life. The sleep spindles reflect the transient bursts of oscillatory activity in the 12-15 Hz range and are generated via corticothalamic networks interacting with the reticular nucleus of the thalamus. Unsurprisingly, sleep spindle frequency is reduced in middle-aged and older adults when compared to young adults. This further increases throughout the night, with the largest age-related impairments being observed up to 50% in the final sleep cycles of the night, as opposed to the faster frequency spindles which are more predominant in young adults. Carrier et al., 2011, De Gennaro and Ferrara, 2003, Mander et al., 2014, Martin et al., 2013, Steriade et al., 1987, Dijk et al., 1989, Landolt et al., 1996.

There are three age-related disruptions in sleep spindles that affect older adults. Firstly, we have reduction in spectral power in the frequency range of sleep spindles generated with the number of sleep spindles declines significantly as you age into your later years. Secondly, the unique features of the spindle waveform are similarly affected as we age and this also appears to contribute to the overall reduction in the signal power that's connected to sleep spindles, with a decrease in the duration, peak, and mean amplitude when you compare older adults to younger adults. Now with slow waves you have these changes are temporally specific to different regions of the brain throughout the night (Fig 1B).De Gennaro and Ferrara, 2003, Mander et al., 2014, Martin et al., 2013,

It's also good to note that age-related reductions in sleep spindles can be readily seen even when the sleep stage in which they wake up doesn't have any changes itself. A good examples would be when you have stage 2 NREM sleep duration not changing but the sleep spindles within stage 2 NREM are reduced. Additionally, make note that the characteristic reduction in total NREM sleep is directly related with the selective loss of stages 3 and 4 of NREM sleep. Thus, even when older adults get the same amount of NREM sleep time, important differences in the density and slow waves can be seen. Therefore, the measurement of NREM sleep stage duration alone cannot capture all of the information with regards to the age-related differences in slow wave expression. De Gennaro and Ferrara, 2003, Fogel et al., 2016, 2016b, Martin et al., 2013, Feinberg and Carlson, 1968, Carrier et al., 2011, Dubé et al., 2015.

All these findings provide evidence for a model in which age-related changes in macro-levels sleep architecture can, and are more often than not, mechanistically distinct from the micro-level changes in sleep oscillations.

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Sleep, Aging, and Gender.

While the differences between younger and older adults with regards to the macro and micro sleep changes is reliably distinct, the degree in which these older adults suffer sleep disruption varies wildly. This large inter-individual variability means that age is not the sole determining factor of sleep disruption in older adults. Other factors that interact with the aging process must then be determining whether older adults will suffer from age-related decline in both sleep quantity and quality.

So we all know that sex has a huge factor on your physiological functions throughout your life. Sex is a key factor with determining levels of sleep disruption with older men suffering from a greater disruption in NREM sleep when compared to women of the same age. A comprehensive study further demonstrates that increasing age is reliably associated with the same detrimental effects previously described: decreased slow wave time, reduced sleep efficiency, increased NREM stage1 sleep time, increased number of waking up, and decreases in REM sleep time (Fig 3). Men over the age of 70 have a 50% reduction in their slow wave sleep when compared to men under the age of 55, while still having an increase in NREM stages 1 and 2. When contrasted against women, there are no significant reductions in slow wave sleep nor increases in NREM sleep times when you compare older and younger women. Now, when you compare men and women, you have men over the age of 70 having more than a 3-fold deficit in slow wave sleep time compared with women of the same age group. Further meta-analyses have replicated these findings of sex-specific differences in slow wave sleep time in older aged adults. While seemingly subject to differences in slow wave sleep time, both men and women showed moderate reductions in REM sleep time, but this suggests that a sex-independent deterioration of this sleep stage. Redline et al., 2004, Ohayon et al., 2004

Sex also causes age-associated changes in slow wave sleep homeostasis, with older men showing significantly less homeostatic slow wave sleep rebound during recovery sleep following sleep deprivation than women of the same age. When you compare basic sleep stages, both older men and women show very similar homeostatic rebounds in REM sleep during post-deprivation nights. Thus sex-dependent and sex-independent effects emerge in older age, which further suggests that some homeostatic mechanisms remain functionally equivalent in both older men and women, like REM sleep, and some are shown to be strongly sex-dependent, like slow wave sleep.Reynolds et al., 1986

Now, when or what age this stratifying sex-dependent effect takes hold is still unclear, with both men and women in their 20’s showing no signs of NREM sleep differences. Although, there is evidence that points to these differences emerging in your mid-30’s with the measurement of SWA. Men in their mid-30’s have been shown to have a divergence which can be seen in the EEG spectral measure of SWA, which is roughly 50% lower in men in their mid-30’s when compared to their 20’s. The same comparison in women is shown to be only about 25% lower in women in their mid-30’s when compared to their 20’s. Further evidence on if and when these gender-dependent changes is sparse and lacking. Ehlers and Kupfer, 1997, Van Cauter et al., 2000

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Sleep is incredibly important, we spend a large portion of our lives sleeping. Understanding the changes on both a macro and micro level is pivotal in further improving your health and what you can expect from growing up in regards to sleep. Furthermore, its been shown that sex does play a role in determining your level of sleep disruption as you age. With this evidence its clear to see that how you sleep is how you age.

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