A 69-year-old man presents to his primary care physician for a general checkup. Overall he is doing well. Since he retired, he has been working on projects at home and taking time to exercise every day. He eats a balanced diet and has been spending time with his wife every evening. Despite this, the patient claims that he feels less well-rested when he wakes up in the morning. The patient states that he used to sleep 9 hours a night in his youth and felt excellent. Now he sleeps 7 hours a night and doesn’t feel as well rested as he used to. The patient’s wife states that he seems to sleep peacefully. His medical history is significant for hypertension and diabetes for which he takes lisinopril and metformin. His temperature is 98.6°F (37°C), blood pressure is 131/85 mmHg, pulse is 71/min, and respirations are 12/min. His neurological exam is within normal limits. The patient is muscular and has a healthy weight with a pleasant demeanor. He denies feeling fatigued or tired currently. Which of the following physiological changes would most likely be seen in this patient?
Increased dopamine
Decreased orexin
Decreased melatonin
Increased norepinephrine
Decreased melatonin
This elderly patient is presenting with sleep that is sufficient but less refreshing than sleep was for him in his past suggesting a diagnosis of normal aging. Melatonin levels naturally decrease as patients age.

Normal aging shortens most phases of sleep. It is normal for melatonin levels to decline during normal aging; however, this change is not responsible for all the symptoms associated with declining quality of sleep. Other changes that occur include decreased REM sleep, decreased stage N3 sleep, and a compensatory increase in stage N2 sleep. Patients will often complain of sleep that is less refreshing than it was in their youth, yet they are still functional and not excessively tired. Treatment is with sleep hygiene though some patients will also benefit from treatment with melatonin supplementation.

Cardinali reviews the role of melatonin in aging. He discusses how natural levels of melatonin decrease in aging animals, which may have implications on the circadian clock. He recommends studies on whether melatonin supplementation may be beneficial to mitigate the effects of aging.

Incorrect Answers:
Answer B: Decreased orexin levels would be seen in patients with narcolepsy, which presents with sudden episodes of falling asleep. This tends to occur in younger patients and is also associated with cataplexy or sudden loss in muscle tone. Treatment of this disorder is with stimulant medications such as modafinil.

Answer C: Increased acetylcholine levels would not be seen in patients as they age and would not explain the changes this patient is experiencing. Rather, acetylcholine levels tend to decline as we age. Drinking caffeinated drinks is associated with increased acetylcholine levels in the brain.

Answer D: Increased dopamine would not be a principle change seen in age-related sleep changes. Higher dopamine levels would increase feelings of being awake as well as alertness. In contrast, decreased dopamine levels can be seen in patients with Parkinson disease, which would present with bradykinesia and a resting tremor.

Answer E: Increased norepinephrine would result in increased wakefulness and potentially insomnia; however, it would not explain the changes seen in normal aging. This chemical is naturally produced during the fight or flight response and can be artificially increased by stimulant drugs such as cocaine.

Bullet Summary:
Normal aging results in a shortening of most phases of sleep as well as decreased melatonin levels and presents with sleep that is subjectively less restful.