The internal clock that drives the daily activities of all living things, from wild flowers to whales, is wound by Earth’s rotation. The 24-hour cycle, tied to one turn of the planet on its axis, embodies a biological clock mimicked by timepieces invented to measure the human day.
But these external clocks don’t exactly match the biological tickings inside ourselves. Many measurements led to the conclusion that the internal clock period is actually closer to 25 hours; that is, the biological clock was thought to drift toward a 25-hour day unless it is set back an hour each day by exposure to morning light and to external clocks. This situation is blamed for a long list of sleep problems.
Now, the most accurate measurements to date, made by researchers at Harvard University, reveal that our natural daily rhythm is much closer to that of other living things than previously believed. The better match opens the way for experts to more effectively treat sleep problems involving night work, jet lag, Earth-orbiting astronauts, or just not being able to go to sleep and wake up on time.
By recording the daily rhythms of hormones and body temperatures in 24 healthy young and old men and women over a one-month period, the researchers conclude that our internal clocks run on a daily cycle of 24 hours, 11 minutes.
But these external clocks don’t exactly match the biological tickings inside ourselves. Many measurements led to the conclusion that the internal clock period is actually closer to 25 hours; that is, the biological clock was thought to drift toward a 25-hour day unless it is set back an hour each day by exposure to morning light and to external clocks. This situation is blamed for a long list of sleep problems.
Now, the most accurate measurements to date, made by researchers at Harvard University, reveal that our natural daily rhythm is much closer to that of other living things than previously believed. The better match opens the way for experts to more effectively treat sleep problems involving night work, jet lag, Earth-orbiting astronauts, or just not being able to go to sleep and wake up on time.
By recording the daily rhythms of hormones and body temperatures in 24 healthy young and old men and women over a one-month period, the researchers conclude that our internal clocks run on a daily cycle of 24 hours, 11 minutes.
Advanced sleep phase syndrome ASPS
also known as the advanced sleep-phase type (ASPT) of circadian rhythm sleep disorder, is a condition in which patients feel very sleepy early in the evening (e.g. 18:00-19:00) and wake up very early in the morning (e.g. 03:00).
ASPS is frequently encountered in the elderly and in post-menopausal women. It can be treated pharmacologically, with evening bright lights, or behaviorally with chronotherapy or free-running sleep.
Familial advanced sleep phase syndrome
In 1999, Louis Ptáček’s research group at the University of California, San Francisco reported findings of a human circadian rhythm disorder showing a familial tendency. The disorder was characterized by a life-long pattern of sleep onset around 7:30pm and offset around 4:30am. Among three lineages, 29 people were identified as affected with this familial advanced sleep-phase syndrome (FASPS), and 46 were considered unaffected. The pedigrees demonstrated FASPS to be a highly penetrant, autosomal dominant trait.[1]
Two years after reporting the finding of FASPS, Ptáček’s and Fu's groups published results of genetic sequencing analysis on a family with FASPS. They genetically mapped the FASPS locus to chromosome 2q where very little human genome sequence was then available. Thus, they identified and sequenced all the genes in the critical interval. One of these was Period2 (Per2). Sequencing of the hPer2 gene revealed a serine-to-glycine point mutation in the CKI binding domain of the hPER2 protein that resulted in hypophosphorylation of Per2 in vitro.[2]
In 2005, Fu's and Ptáček’s labs reported discovery of a different mutation causing FASPS. This time, CKIδ was implicated, demonstrating an A-to-G missense mutation that resulted in a threonine-to-alanine alteration in the protein.[3] The evidence for both of these reported causes of FASPS is strengthened by the absence of said mutations in all tested control subjects and by demonstration of functional consequences of the respective mutations in vitro. Fruit flies and mice engineered to carry the human mutation also demonstrated circadian phenotypes although the mutant flies had a long circadian period while the mutant mice had a shorter period.[2][3] The differences between flies and mammals that account for this difference are not known. Most recently, Ptáček and Fu reported additional studies of the human Per2 S662G mutation and generation of mice carrying the human mutation. These mice had a circadian period almost 2 hours shorter than wild-type animals. Genetic dosage studies of CKIδ on the Per2 S662G mutation revealed that CKIδ is having opposite effects on Per2 levels depending on the sites on Per2 that CKIδ is phosphorylating
ASPS is frequently encountered in the elderly and in post-menopausal women. It can be treated pharmacologically, with evening bright lights, or behaviorally with chronotherapy or free-running sleep.
Familial advanced sleep phase syndrome
In 1999, Louis Ptáček’s research group at the University of California, San Francisco reported findings of a human circadian rhythm disorder showing a familial tendency. The disorder was characterized by a life-long pattern of sleep onset around 7:30pm and offset around 4:30am. Among three lineages, 29 people were identified as affected with this familial advanced sleep-phase syndrome (FASPS), and 46 were considered unaffected. The pedigrees demonstrated FASPS to be a highly penetrant, autosomal dominant trait.[1]
Two years after reporting the finding of FASPS, Ptáček’s and Fu's groups published results of genetic sequencing analysis on a family with FASPS. They genetically mapped the FASPS locus to chromosome 2q where very little human genome sequence was then available. Thus, they identified and sequenced all the genes in the critical interval. One of these was Period2 (Per2). Sequencing of the hPer2 gene revealed a serine-to-glycine point mutation in the CKI binding domain of the hPER2 protein that resulted in hypophosphorylation of Per2 in vitro.[2]
In 2005, Fu's and Ptáček’s labs reported discovery of a different mutation causing FASPS. This time, CKIδ was implicated, demonstrating an A-to-G missense mutation that resulted in a threonine-to-alanine alteration in the protein.[3] The evidence for both of these reported causes of FASPS is strengthened by the absence of said mutations in all tested control subjects and by demonstration of functional consequences of the respective mutations in vitro. Fruit flies and mice engineered to carry the human mutation also demonstrated circadian phenotypes although the mutant flies had a long circadian period while the mutant mice had a shorter period.[2][3] The differences between flies and mammals that account for this difference are not known. Most recently, Ptáček and Fu reported additional studies of the human Per2 S662G mutation and generation of mice carrying the human mutation. These mice had a circadian period almost 2 hours shorter than wild-type animals. Genetic dosage studies of CKIδ on the Per2 S662G mutation revealed that CKIδ is having opposite effects on Per2 levels depending on the sites on Per2 that CKIδ is phosphorylating
Circadian rhythm abnormalities
Non-24-hour sleep-wake syndrome and other persistent circadian rhythm sleep disorders are believed to be caused by an inadequate ability to reset the sleep/wake cycle in response to environmental time cues. These individuals' circadian clocks might have an unusually long cycle, and/or might not be sensitive enough to time cues. People with DSPS, more common than Non-24, do entrain to nature's 24 hours, but are unable to sleep and awaken at socially preferred times, sleeping instead, for example, from 4 a.m. to noon. According to doctors Cataletto and Hertz at WebMD, "Altered or disrupted sensitivity to zeitgebers is probably the most common cause of circadian rhythm disorder.
Non-24-hour sleep-wake syndrome and other persistent circadian rhythm sleep disorders are believed to be caused by an inadequate ability to reset the sleep/wake cycle in response to environmental time cues. These individuals' circadian clocks might have an unusually long cycle, and/or might not be sensitive enough to time cues. People with DSPS, more common than Non-24, do entrain to nature's 24 hours, but are unable to sleep and awaken at socially preferred times, sleeping instead, for example, from 4 a.m. to noon. According to doctors Cataletto and Hertz at WebMD, "Altered or disrupted sensitivity to zeitgebers is probably the most common cause of circadian rhythm disorder.
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