THE SCIENCE OF SLEEP: Exploring the Link Between Rest, NAD and Aging
Diana
Published in Bloodo Blog · 7 min read · June 13, 2025
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What if one molecule could influence your sleep, energy, and even aging? It’s called NAD—short for nicotinamide adenine dinucleotide—and it’s more powerful than you might think.
We’ve already explored what NAD is and its role in longevity. Today, we’ll take a closer look at how NAD affects sleep and how both sleep and NAD are connected to healthy aging and more energized life.
Understanding Sleep Cycles
Before diving into the connection between NAD and sleep, let’s quickly review how sleep works. Sleep occurs in cycles, each lasting around 90 to 110 minutes, and consists of two main types: rapid eye movement (REM) and non-REM (NREM) sleep. NREM is divided into three stages, which are then followed by REM, where vivid dreaming takes place.1
How Does NAD Impact Sleep at the Cellular Level?
NAD fuels important enzymes in our body, including two major groups: sirtuins (SIRTs) and poly (ADP-ribose) polymerases (PARPs).
SIRTs are conserved proteins that remained similar across different species throughout evolution. They have caught the attention of researchers for their role in slowing down the aging process. SIRTs are key regulators of several longevity-associated biological processes, including genetic material (DNA) repair, autophagy, inflammation, oxidative stress response, and metabolism.2 They help protect cells by delaying telomere shortening, which is a well-known indicator of cellular aging (called cellular senescence) and the aging process in organisms.3,4
PARPs are another group of enzymes that also help repair DNA and take care of how our genetic material is organized and used. PARPs play key roles in DNA synthesis, chromatin structure, transcription, replication, and recombination.5
Sirtuin (SIRT1) and Sleep Regulation
NAD is involved in regulating circadian rhythms, which control our sleep-wake cycle. These rhythms determine when we sleep and when we wake up, and their proper regulation is essential for optimal rest. SIRT1, the most studied sirtuin in mammals, helps regulate sleep by interacting with wake-sleep neurotransmitters and sleep-promoting molecules called somnogens.6 When NAD levels are low, SIRT1 becomes less effective, potentially disrupting sleep quality and leading to sleep issues.
The Role of NAD in Sleep Pressure
Another key concept is sleep pressure (also known as homeostatic sleep pressure), which is the body’s natural drive to fall asleep. This drive builds during wakefulness as certain substances accumulate in the brain. A key player here is PARP1, a NAD-dependent enzyme.
In mice: Blocking PARP1 increased wakefulness, reduced NREM sleep, and lowered sleep intensity.
In zebrafish: Boosting PARP1 increased sleep duration, while inhibiting it shortened sleep.
This suggests PARP1 helps regulate sleep by increasing sleep pressure.1
The Cost of Restless Nights
What happens when all these hard-working molecules don’t function properly? Ever stayed up late and paid the price the next day? Sure, one sleepless night might leave you cranky, but it’s not the end of the world. The real danger is chronic sleep deprivation, which silently chips away at your health, increasing your risk of heart disease, diabetes, obesity, and mental health issues.7
Research shows that sleep and circadian rhythms influence immune functions that are easily disrupted by sleep disorders. Sleep fragmentation also triggers hormonal changes, including increased glucocorticoids and sympathetic nervous system activity, which stimulate energy release.
These disruptions affect cellular energy production. Inside each cell, mitochondria act like tiny factories. When overwhelmed, they release reactive oxygen species (ROS), which can damage mitochondrial and nuclear DNA. If unrepaired, this damage leads to telomere shortening and accelerates cellular aging.8
Sleep Deprivation and DNA Damage
In one study, older adults who slept only 4 hours showed a noticeable increase in DNA damage response gene activity. Alarmingly, this change remained even after a full night of recovery sleep.9
Another large study analyzed data from 336,559 UK Biobank participants. It found a surprising link between sleep duration and biological aging.
Both short and long sleep durations were associated with a higher risk of accelerated aging, compared to the optimal 6–8 hours per night. Interestingly, short sleepers had a slightly lower risk than long sleepers.10
These findings emphasize the importance of a balanced sleep routine—not too little, not too much.
The Power of NAD-Dependent Enzymes in DNA Repair
While poor sleep has harmful effects, our cells have a built-in repair system powered by NAD-dependent enzymes like SIRTs and PARPs.
PARP1 detects and repairs DNA strand breaks.¹¹
SIRT1 supports this process by modifying histones, proteins that help package DNA in the cell. When DNA is damaged, SIRT1 removes small chemical tags from histones, allowing the repair process to proceed
Everything in the body is interconnected. Prolonged wakefulness increases DNA damage, but sleep promotes repair.¹³ Sleep activates genes involved in DNA repair, showing just how essential it is for cellular health. NAD doesn’t directly fix the damage, but it enables the systems that do. Without it, repair cannot happen properly.
Curious how this all ties into brain health and cognitive longevity? Stay tuned—we’ll explore that next, along with the latest research on how to optimize your rest for a longer, healthier life.
Disclaimer This blog is for informational purposes only and is not intended as medical advice. Always consult a qualified healthcare professional before making changes to your health routine, including supplements, diet, or sleep habits. Research on NAD is ongoing, and findings are still developing. Individual results may vary.
1. Feltes, B. C. & Alvares, L. de O. PARP1 in the intersection of different DNA repair pathways, memory formation, and sleep pressure in neurons. J. Neurochem.168, 2351–2362 (2024).
2. You, Y. & Liang, W. SIRT1 and SIRT6: The role in aging-related diseases. Biochim. Biophys. Acta – Mol. Basis Dis.1869, 166815 (2023).
3. Vazquez, B. N., Thackray, J. K. & Serrano, L. Sirtuins and DNA damage repair: SIRT7 comes to play. Nucleus8, 107–115 (2017).
4. Palacios, J. A. et al. SIRT1 contributes to telomere maintenance and augments global homologousrecombination. J. Cell Biol.191, 1299–1313 (2010).
5. Zhu, H., Tang, Y.-D., Zhan, G., Su, C. & Zheng, C. The Critical Role of PARPs in Regulating Innate Immune Responses. Front. Immunol.12, (2021).
6. Mehramiz, M., Porter, T., Laws, S. M. & Rainey-Smith, S. R. Sleep, Sirtuin 1 and Alzheimer’s disease: A review. Aging brain2, 100050 (2022).
7. Colten, H. R. & Altevogt, B. M. Sleep disorders and sleep deprivation: An unmet public health problem. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem (2006). doi:10.17226/11617.
8. Carroll, J. E. & Prather, A. A. Sleep and Biological Aging: A Short Review. Curr. Opin. Endocr. Metab. Res.18, 159–164 (2021).
9. Carroll, J. E. et al. Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans. Brain. Behav. Immun.51, 223–229 (2016).
10. Wang, M. et al. Association between sleep traits and biological aging risk: a Mendelian randomization study based on 157 227 cases and 179 332 controls. Sleep47, 1–11 (2024).
11. Zada, D. et al. Parp1 promotes sleep, which enhances DNA repair in neurons. Mol. Cell81, 4979-4993.e7 (2021).
12. Mei, Z. et al. Sirtuins in metabolism, DNA repair and cancer. J. Exp. Clin. Cancer Res.35, 182 (2016).
13. Bellesi, M., Bushey, D., Chini, M., Tononi, G. & Cirelli, C. Contribution of sleep to the repair of neuronal DNA double-strand breaks:evidence from flies and mice. Sci. Rep.6, 36804 (2016).
THE SCIENCE OF SLEEP: Exploring the Link Between Rest, NAD and Aging
What if one molecule could influence your sleep, energy, and even aging? It’s called NAD—short for nicotinamide adenine dinucleotide—and it’s more powerful than you might think.
We’ve already explored what NAD is and its role in longevity. Today, we’ll take a closer look at how NAD affects sleep and how both sleep and NAD are connected to healthy aging and more energized life.
Understanding Sleep Cycles
Before diving into the connection between NAD and sleep, let’s quickly review how sleep works. Sleep occurs in cycles, each lasting around 90 to 110 minutes, and consists of two main types: rapid eye movement (REM) and non-REM (NREM) sleep. NREM is divided into three stages, which are then followed by REM, where vivid dreaming takes place.1
How Does NAD Impact Sleep at the Cellular Level?
NAD fuels important enzymes in our body, including two major groups: sirtuins (SIRTs) and poly (ADP-ribose) polymerases (PARPs).
Sirtuin (SIRT1) and Sleep Regulation
NAD is involved in regulating circadian rhythms, which control our sleep-wake cycle. These rhythms determine when we sleep and when we wake up, and their proper regulation is essential for optimal rest. SIRT1, the most studied sirtuin in mammals, helps regulate sleep by interacting with wake-sleep neurotransmitters and sleep-promoting molecules called somnogens.6 When NAD levels are low, SIRT1 becomes less effective, potentially disrupting sleep quality and leading to sleep issues.
The Role of NAD in Sleep Pressure
Another key concept is sleep pressure (also known as homeostatic sleep pressure), which is the body’s natural drive to fall asleep. This drive builds during wakefulness as certain substances accumulate in the brain. A key player here is PARP1, a NAD-dependent enzyme.
This suggests PARP1 helps regulate sleep by increasing sleep pressure.1
The Cost of Restless Nights
What happens when all these hard-working molecules don’t function properly? Ever stayed up late and paid the price the next day? Sure, one sleepless night might leave you cranky, but it’s not the end of the world. The real danger is chronic sleep deprivation, which silently chips away at your health, increasing your risk of heart disease, diabetes, obesity, and mental health issues.7
Research shows that sleep and circadian rhythms influence immune functions that are easily disrupted by sleep disorders. Sleep fragmentation also triggers hormonal changes, including increased glucocorticoids and sympathetic nervous system activity, which stimulate energy release.
These disruptions affect cellular energy production. Inside each cell, mitochondria act like tiny factories. When overwhelmed, they release reactive oxygen species (ROS), which can damage mitochondrial and nuclear DNA. If unrepaired, this damage leads to telomere shortening and accelerates cellular aging.8
Sleep Deprivation and DNA Damage
In one study, older adults who slept only 4 hours showed a noticeable increase in DNA damage response gene activity. Alarmingly, this change remained even after a full night of recovery sleep.9
Another large study analyzed data from 336,559 UK Biobank participants. It found a surprising link between sleep duration and biological aging.
Both short and long sleep durations were associated with a higher risk of accelerated aging, compared to the optimal 6–8 hours per night. Interestingly, short sleepers had a slightly lower risk than long sleepers.10
These findings emphasize the importance of a balanced sleep routine—not too little, not too much.
The Power of NAD-Dependent Enzymes in DNA Repair
While poor sleep has harmful effects, our cells have a built-in repair system powered by NAD-dependent enzymes like SIRTs and PARPs.
Everything in the body is interconnected. Prolonged wakefulness increases DNA damage, but sleep promotes repair.¹³ Sleep activates genes involved in DNA repair, showing just how essential it is for cellular health. NAD doesn’t directly fix the damage, but it enables the systems that do. Without it, repair cannot happen properly.
Curious how this all ties into brain health and cognitive longevity? Stay tuned—we’ll explore that next, along with the latest research on how to optimize your rest for a longer, healthier life.
This blog is for informational purposes only and is not intended as medical advice. Always consult a qualified healthcare professional before making changes to your health routine, including supplements, diet, or sleep habits. Research on NAD is ongoing, and findings are still developing. Individual results may vary.