Postpartum sleep loss and accelerated epigenetic aging

Abstract

Background

Insufficient sleep has been linked to accelerated biological aging in adults, providing a possible mechanism through which sleep may influence disease risk. In the current paper, we test the hypothesis that short sleep in postpartum would predict older biological age in women one year post birth, as indicated by accelerated epigenetic aging.

Methods

As part of a larger study of pregnancy and postpartum health (Healthy Babies Before Birth, HB3), 33 mothers provided blood samples for epigenetic aging clock estimates. intrinsic epigenetic age acceleration (IEAA), extrinsic apigenetic age acceleration, phenotypic epigenetic age acceleration (PEAA), GrimAge, DNAmPAI-1, and DNAm telomere length (TL) were calculated using established protocols. Sleep duration was categorized as insufficient sleep (<7 hours per night) or healthy sleep duration (7+ hours per night). Sleep quality was determined using the Pittsburgh Sleep Quality Index (Global score >5).

Results

Maternal postpartum sleep duration at 6 months, but not 12 months, following a birth was predictive of older 12-month IEAA, B (SE) = 3.0 (1.2), P = .02, PEAA, B (SE) = 7.3 (2.0), P = .002, and DNAmTL, B (SE) = −0.18 (0.07), P = .01, but not other indices, all P> .127. Self-reported poor sleep quality at 6 and 12 months was not significantly related to epigenetic age.

Conclusions

These findings suggest that insufficient sleep duration during the early postpartum period is associated with accelerated biological aging. As the sample size is small, additional research is warranted with a larger sample size to replicate these findings.

Introduction

Parenting of infants and young children is typically accompanied by routine sleep disruptions, often resulting in insufficient sleep for the parents. In the first 6 months of life, in particular, infant sleep patterns are wrought with nighttime awakenings, mostly due to frequent feedings, a responsibility that often falls on mothers.¹ Thus, for many mothers, postpartum is a time of poor sleep quality and shortened sleep duration.^2,3 Although there is evidence that this disjointed and insufficient sleep during postpartum impacts daytime functioning, including increased fatigue, mood disturbances, and sleepiness,^1,2,4 the impact of postpartum sleep disruptions on biological processes related to health and disease is less clear. A considerable body of research has demonstrated that inadequate sleep and chronic poor sleep quality increase vulnerability to age-related disease and early death risk,5., 6., 7., 8., 9., 10., 11., 12. with evidence that inflammatory pathways are likely involved.¹³ However, limited research has examined sleep in the context of postpartum biological aging. Addressing whether routine sleep insufficiency may be detrimental for health by accelerating biological aging provides novel insight into this normative challenge during early parenthood and provides evidence for the importance of interventions that might target sleep in this context.¹⁴

Several molecular mechanisms that drive increased health risk as a result of insufficient sleep have been proposed, including inflammation, declines in physiological system function, and recently, accelerated biological aging.^13,15., 16., 17. Rates at which a person ages at the biological level is an important indicator for later risk for morbidity and mortality,^18,19 whereas identifying factors that influence biological aging may prove to prevent or delay the onset of disease.^20,21 For example, a single night of experimental partial sleep deprivation in older adults activated genes consistent with biological aging pathways, including increasing inflammation, DNA damage, and cellular senescence.^13,22,23 In mouse models, repeated disruption of sleep altered biological aging processes, including increasing cellular stress, injury, and senescence.24., 25., 26. Short sleep duration, poor sleep quality, and diagnosed insomnia have also been linked to shorter leukocyte telomere length, a marker of biological aging, in varied populations of mid- to late-life adults.27., 28., 29., 30., 31., 32., 33. These findings highlight plausible molecular mechanisms through which insufficient sleep impacts risk for later disease.

In addition to telomere length, the epigenetic clock has been proposed to serve as an estimate of biological age. Several methods of calculating epigenetic clock indicators have been proposed,34., 35., 36. including (1) extrinsic epigenetic age acceleration (EEAA),^16,34,35 (2) intrinsic epigenetic age acceleration (IEAA), (3) phenotypic epigenetic age acceleration (PEAA),³⁶ (4) GrimAge, and (5) DNAm plasminogen activator inhibitor-1 (PAI-1).³⁷ Recently, the methylation data have also been used to derive an estimate of telomere length in the sample,⁶ called DNA methylation telomere length (DNAmTL). Together these measures were designed to capture cellular aging and age-related disease risk. Several large epidemiological investigations have used estimates of DNA methylation based biological clocks to estimate biological age and predict important outcomes, namely, mortality,^37,38 physical fitness,³⁹ and disease risk.⁴⁰ PEAA in particular has been defined as a predictor of physical (ie, phenotypic signs) of aging and tracks with multiple biological indictors of disease risk,³⁶ suggesting that these epigenetic clock estimates are useful in tracking the aging process itself and not just lifespan.

Although the existing literature provides initial links between sleep quality and short sleep duration with molecular markers of biological aging, to date the research is limited to adults in mid- to late life. This limits our current knowledge as to whether sleep impacts rates of biological aging in younger adults, such as women of reproductive age. In the current study, we conducted a secondary analysis of pregnant women recruited from a larger study and followed them over 1-year postpartum. We proposed that mothers with significant insufficient sleep during the postpartum period (6 months after pregnancy) would have an accelerated epigenetic age at 1 year after pregnancy.