Dr Catherine de Goursac
A dual perspective from two scientific experts on this major biological milestone Sleep, governed by the circadian clock, alternates between light, deep and paradoxical phases, each ensuring physical recovery, memory consolidation and emotional balance.
Advances in research on the glymphatic system (brain washing) and orexin are guiding the management of insomnia, particularly in older adults.
Sleep architecture: physiological overview
Light sleep (N1–N2) represents the gateway to sleep: muscle relaxation, progressive slowing of brain waves and sensory disengagement. Deep sleep (N3) constitutes the restorative phase: secretion of growth hormone, immune regulation, energy restoration and activation of the glymphatic system, a key mechanism for the nocturnal elimination of neuronal waste. Paradoxical sleep (REM), with high cerebral activity, contributes to memory consolidation, emotional regulation and synaptic plasticity. This architecture evolves throughout life: polyphasic sleep rich in REM in infants, a frequent deficit of N3 in adolescents, and progressive fragmentation in older adults with a marked reduction in N3 and REM sleep.
History and modernity: from biphasic sleep to the screen era
Before industrialisation, human sleep was biphasic, alternating a “first sleep”, a period of nocturnal wakefulness (reading, prayer, social interactions), followed by a “second sleep”. The advent of artificial lighting and modern lifestyles compressed this pattern into a monophasic nocturnal sleep. Today, average sleep duration is around 7 hours, compared with 8–9 hours in pre-industrial times.
Melatonin: circadian, anticancer and neuroprotective roles
Melatonin is produced by the pineal gland from serotonin. Light inhibits its secretion, while darkness activates it.
1. Circadian role and aging
Melatonin secretion decreases with age (its synthesis declines from the age of 40!), and in Alzheimer’s disease this decline is early and severe.
2. Neuroprotective properties
Numerous studies highlight:
• Powerful antioxidant activity, reducing oxidative stress, a major factor in neurodegeneration.
• Anti-amyloid effect: inhibition of aggregation and facilitation of β-amyloid peptide clearance (Pappolla et al., 1998).
• Anti-tau effect: reduction of hyperphosphorylation.
• Circadian regulation, improving cognition and behaviour.
Melatonin also plays a potential protective role against breast cancer, via anti-oestrogenic, antioxidant and circadian-regulating mechanisms. Night work, by inhibiting melatonin, is associated with an increased risk of cancer and cognitive decline.
“Brain washing”: the glymphatic system
The glymphatic system, discovered by Nedergaard in 2012, is a neuronal waste clearance network that functions almost exclusively during deep sleep.
Astrocytes, via cerebrospinal fluid, “clean” the interstitial spaces and eliminate:
• β-amyloid,
• tau protein,
• inflammatory metabolites.
Severe stress, inflammation or sleep deprivation disrupt this system. Chronic sleep deprivation leads to β-amyloid accumulation. A major meta-analysis (Bubu et al., 2017) shows that fragmented sleep significantly increases the risk of Alzheimer’s disease.
Sleep, inflammation and psychological vulnerability
In 2025, a major study (Irwin et al., JAMA Psychiatry, 2025) demonstrated that older adults with insomnia exposed to inflammatory stress have a threefold increased risk of depression. Chronic sleep deprivation weakens the blood–brain barrier, allowing cytokines and immune cells to pass through, thereby intensifying cerebral inflammation and promoting depressive symptoms.
Therapeutic approaches: 2026 update
1. Non-pharmacological approaches (first-line)
• Exposure to natural light in the morning, at midday and in the evening: circadian anchoring.
• Biological synchronisation: regular wake-up and bedtime schedules, respect for chronotype. Pre-sleep routine reducing auditory and light stimuli.
• Adapted physical activity.
• Reduction of long daytime naps.
• CBT-I (cognitive behavioural therapy for insomnia): validated first-line treatment in all international recommendations.
2. Pharmacological approaches and innovations
Prolonged-release melatonin (2–10 mg)
Useful in older adults with nocturnal awakenings. Few side effects.
Conventional hypnotics
Benzodiazepines and related drugs: rapid efficacy but risk of dependence, long-term cognitive impairment, reduction of brain washing; must be strictly limited.
Orexin receptor antagonists (DORAs): a therapeutic revolution
The orexin system (OX1R / OX2R), located in the hypothalamus, is a central regulator of wakefulness and vigilance.
1. Mechanism of action
DORAs simultaneously block OX1R and OX2R → reduction of wakefulness → initiation and maintenance of sleep. Daridorexant (Quviviq®) is the most recent DORA, designed with a short half-life (≈ 8 hours) in order to preserve optimal wakefulness the following day.
• Significant improvement in total sleep time.
• Reduction in wake time after sleep onset, with easy return to sleep in the second half of the night.
• Improvement in daytime quality of life (IDSIQ score).
2. Advantages
• Induction of sleep close to physiological sleep, unlike conventional hypnotics.
• No global CNS inhibition → lower risk of falls or confusion.
• Low risk of dependence, no significant rebound effect.
• Significant improvement in daytime wakefulness quality (particularly demonstrated for daridorexant).
• Increase in brain washing.
Sleep is essential for maintaining cerebral, immune and psychological health. Recent discoveries regarding the glymphatic system and the central role of orexin are transforming our understanding of the link between sleep, neuroprotection and aging. In 2025, DORAs represent a major therapeutic advance. L
References
*Platysma Bands: Is a Change Needed in the Surgical Paradigm? Trévidic P, Criollo-Lamilla G. Plast Reconstr Surg. 2017 Jan;139(1):41-47. doi: 10.1097/PRS.0000000000002894
** Surgical Denervation of Platysma Bands: A Novel Technique in Rhytidectomy. Trévidic P, Criollo-Lamilla G. Plast Reconstr Surg. 2019 Nov;144(5):798e-802e. doi: 10.1097/PRS.0000000000006148.
*** Denervation Neck Lift: An Updated Rhytidectomy Technique and Prospective Follow-Up of 80 Patients. Criollo-Lamilla G, Trévidic T, Imanilov A, Trévidic P. Facial Plast Surg. 2025 Jun 17. doi: 10.1055/a-2624-7946
Dr Catherine de Goursac
Expert in medical aesthetic techniques for 30 years. Teacher at the faculty of medicine since 2017, board member of the AFME (French Association of Aesthetic Medicine) and the FSMEA (Union of Aesthetic and Anti-aging Doctors). Permanent member of the French Society of Aesthetic Medicine.
Infos: esthetiquemedicale.com
