>> Good morning, everybody.
I want to start by thanking the two co-chairs
for inviting me.
What a incredible honor to be the only XY
embedded among all the XX.
Too bad I'm not younger and too bad I'm not available.
So, I've been tasked with the charge
of discussing chronobiology,
and how biological rhythms may affect you.
What a great topic.
Sleep effects not just XXs, but also XYs.
It's a universal, physiological problem,
a process rather, that is relevant.
It's relevant for every functional aspect of our lives.
Biological, psychological, or otherwise.
So what I thought I would do
is just break it down into two large pieces.
First, just talk a little bit about chronobiology.
What does it really mean
when we use that term chronobiology?
And then, talk a little bit about sleep issues.
Sleep itself is a very large topic,
like many other conditions and physiologic systems,
so not sure if I'll do it justice within 20 minutes,
or even 10 for that matter, but I will give it my best shot.
So, chronobiology, what is it?
Well, chronobiology is the study of biological rhythms.
Everything has a rhythm.
Sleep wake is one example of a rhythm.
Your sleep cycle and your wake cycle is a 24 hour cycle,
and therefore a circadian cycle.
Eese, I need to get closer.
I think it's the XX versus XY fear.
Oh, I think it's moving also,
and that's another problem.
Anyway, so sleep and wake is one example
of a biological rhythm, which is a kind of 24 hour cycle,
and therefore we tend to call it a circa,
circadian rhythm, something that's around 24 hours in cycle.
But there are other types of biological rhythms.
There are rhythms that are shorter than 24 hours,
and there are rhythms that are longer than 24 hours.
One obvious rhythm that's longer than 24 hours
is the menstrual cycle.
It's many, many days, if not weeks, in fact.
So, there are different types of biological rhythms.
Temperature, another type of biological rhythm.
Mood, alertness,
psychological well being.
Manual dexterity.
All of these have biological rhythms,
and they have cyclicity during the course of the day.
So there's a lot that's really integrated
into what we consider the field of chronobiology.
So I thought what I would do is
at least introduce you to where all these rhythms originate.
Over the last two to three decades,
we now know that these biological rhythms
are coordinated by an area of the brain
which is known as a super chiasmic nucleus.
This is a small area of the brain,
located near the hypothalamus,
which really also regulates other biological systems.
Eating, mating, in some animals.
Biological rhythms are present in every species
that we know of, and in fact,
we also now know, biological rhythms are present
at the level of the cell.
Cells themselves, independent of the entire
in vivo system, as we would call it, have rhythms.
Protein expression at the cellular level
varies as a function of time of day.
Now, these biological rhythms are controlled
by this area of the brain called the super chiasmic nucleus.
Now this area of the brain receives inputs
from many different sources.
One of the most simplest and the strongest stimulus,
often called a zeitgeber, a German word for time giver,
is sunlight.
Sunlight, because of it's input to the brain
regulates how the biological systems will cycle.
So, one abhorrency that all of you know
is when you shift from one time zone to the other
exposure to sunlight changes.
And that does have an impact in biological systems,
and I'll tell you how some of these systems
get deranged when you move from one time zone to the other.
But one key time giver, or zeitgeber, is sunlight.
But there are other time givers.
Activity levels, meals, and your own behavior
entrains this super chiasmic nucleus
to maintain that sort of 24 hour cycle.
So, to some degree you are in control
of your biological systems.
Obviously, part of your systems is not under your control,
because it has to be entrained,
it has to be shifted over time.
Therefore, you cannot just go to London
or Asia and say, well, I'm gonna go to bed at this time,
because there's an intrinsic, underlying,
entrained system that's controlling your sleep-wake
and other biological systems.
Now, how do we measure what your system is doing?
How do we actually figure it out?
Well, there's no direct way to measure the activity
of the super chiasmic nucleus.
The many things that we do,
obviously, the activity meters that we do,
are a surrogate of how we actually track biological systems.
We track activity, and therefore from activity,
we're even tracking temperature,
infer where we are in our biological systems.
Now the super chiasmic nucleus
and its effect downstream
on many different biological systems
controls much about ourselves.
Thyroid hormone, growth hormone, cortisol.
These very significant hormones
that control other biological systems
are controlled by this sort of central pacemaker
in the super chiasmic nucleus.
Cortisol, for example, will peak in the morning.
Thyroid function, or growth hormone,
have different areas in the night.
Growth hormone, for example,
peaks during sleep,
and is higher in the earlier parts of the night.
So these biological systems are being controlled
by a central pacemaker,
which is then being controlled
by extrinsic sunlight behavior.
And you can change it to some degree,
but not completely, because there is an intrinsic pacemaker.
Now what happens if this super chiasmic nucleus goes kaput?
Well, what happens is you actually get a derangement,
and you can get into what's called a free running cycle.
What that basically means is the super chiasmic nucleus,
the pacemaker that controls it is no longer present,
and the individuals continue to just drift,
there's no entrainment.
Will drift over time and they'll be no rhythm per se at all.
They're unable to really regulate themselves.
So, lesions, of the super chiasmic nucleus,
at least in animal studies,
have really shown very nicely
how some of the disorders that we see of circadian systems
can come about.
One of the most common circadian disturbances
that we see in clinical practice
is young individuals that are unable to go to bed
at an earlier hour.
They can't fall asleep til two, three in the morning.
That is called circadian phase delay,
cause they're delayed.
These are your teenagers, and usually young adults.
As we age, there is a natural tendency
for the super chiasmic nucleus to shift.
So, most of us, as we get older,
into our sixties, seventies, will tend to go to bed earlier,
and won't be able to sleep beyond four or five.
And that's natural, biological aging.
It's happening to me.
This conference at nine o'clock,
I was up at five o'clock thinking why can't I go to bed?
Aging, the natural, biological system
is really shifting.
So, with age, we become phase advanced.
What that really means is the natural,
average time for bed is 11 to, let's say six.
The clock shifts counter-clockwise as we get older.
In younger adults, the clock has shifted clockwise,
so they go to bed, like my teenage daughter,
at two am, and can sleep til 12 in the afternoon.
I can't do that.
I just can't.
But I can manipulate that cycle if you know how to do it.
So, folks like us, that are aging,
will have this shift.
This counter-clock rotation in our circadian rhythms,
with regards to when we will be able to go to bed,
when we'll wake up.
So, one of the common things we see in clinical practice
is folks coming to us and saying
I wake up at four in the morning
and I can't go back to sleep.
When you dive into them a little further,
when you do a little deep dive,
you'll learn that they think
that they still have those older habits,
where they stay up and watch the late night show,
til about 11.
So, what happens is, because of their behavior,
they're used to those schedules that they maintain,
these days it's the internet,
you know, you check your emails,
you do your work until 11, 12,
but you forget the fact,
or you're unaware of the fact
that you're supposed to really go to bed earlier
because your biological system needs to go to bed earlier.
But then you wake up at four and say,
well, I can't go back to sleep.
So, what happens to most of these folks?
They go to some primary care doctor,
who doesn't recognize the phase shifting that's occurred,
and medications get started
that are used to make an individual fall asleep.
But what you really needed is a little more
education on the biological rhythmicity
and it's rotation that's happening.
Instead of using a drug,
we can use other things like sunlight
to actually a bit to the right side,
or clockwise, in these individuals.
So, individuals that are phase advanced as we get older.
How many have phase advance the way I've described it?
Go to bed early and then wake up early
and can't go back to sleep.
Yeah, why not?
Why am I not surprised?
So, the wrong thing for you is really a medication
for example, that will make you fall asleep.
The right thing for you to do is evening sunlight exposure.
Something simple as that.
So, you can imagine how sunlight really has an impact.
And when you start thinking about disorders,
like Seasonal Affective Disorder.
Now that's very common.
It's worse in the winter time.
Guess what, because the sunlight is absent,
and we really don't get that input that we need.
So, these biological systems of sleep wake, hormonal,
have such a direct impact
on every functional state in our body
that it is often also neglected.
So that tells me I'm about halfway into my talk,
and now it's 10 minutes.
The rest of the 10 minutes I'll tell you
what happens when sleep,
perhaps through biological perturbations
of the circadian system, or other reasons,
get disturbed.
Sleep.
Just talk about sleep.
Sleep also has a rhythm.
Sleep has a rhythm that is ultradian.
What that means, it's less than 24 hours.
Now, it's not as simple as you turn the lights off,
your head goes to the pillow and you're done.
It's not as simple as that.
When your head goes to the pillow
there's a cycling of sleep internally,
to those eight hours that you're in bed.
The earlier stages are called non Rapid Eye Movement sleep,
and the later stages, the later part of the night,
you see what's called Rapid Eye Movement sleep.
Now, non Rapid Eye Movement sleep,
or non REM sleep, has some very interesting characteristics.
We discriminate those based on what we see
in the brain wave activity that we can measure
in a sleep lab.
Non REM activity, earlier part of the night,
has things like growth hormone secretion.
REM, REM sleep, that occurs in the latter part of the night
is where vivid dreaming can occur.
So, if you remember a dream,
most likely you were awakened during REM sleep.
So, sleep itself has these rhythms.
And how does it have these rhythms?
You have multiple episodes of REM sleep.
It's not just non REM and REM and you're done,
it's non REM, a little bit of REM,
then non REM again, a little more REM.
And in fact, the rhythm of REM increases
over the duration of REM increases
as you go through the night.
Where REM cycles in healthy individuals like us
will be the longest in the latter part of the night.
So, even within the cycle of sleep,
the eight hours that you sleep,
there is a rhythmicity to that,
and that's called an ultradian cycle.
Now, sleep can be disturbed by many things.
I can go to London,
now we've got a common phenomena of jet lag.
Right, very simple thing, we go to California,
we have the other problem.
Going east and going west are very different.
It's easier, as you know, to go west.
It's nice, we can actually,
we have the ability to expand our clocks.
We have a very difficult time to contract our clocks.
What that means is, if I were to go to London right now,
it's about three pm.
In about six hours, they will be going to bed,
six or seven hours.
But, roughly my time it will be about three pm.
I can't go to bed at 3 pm.
So, it's difficult to really contract our clocks,
but it's easier to expand,
therefore westward travel's
often easier than eastward travels.
Some of you don't know, actually,
this difference in performance
has been used by baseball teams to figure out
which way they're going to be more likely to win or lose.
This has been actually shown.
A very nice article in the Journal of Science
showing that traveling one direction
versus traveling the other direction
does change the probability
of someone actually losing or winning a baseball game.
So, alertness, functionality is dependent
on these biological rhythms.
When these biological rhythms
are either naturally, or perhaps artificially interrupted,
or naturally being circadian phase delay, the teenager,
you circadian phase advanced older,
sort of maturing individual,
these are natural biological processes
that are perturbing the circadian system.
But we can also perturb it artificially, we can get up.
We can get up at four and go for a drive, go to work.
That's not the best thing.
We now know when you actually interfere with these systems,
you can create some really grave consequences.
The highest risk for accidents is guess where?
Four o'clock in the morning.
Not a good time to drive out there.
These biological systems not only impair
our functional capacity,
they also impact how we handle other things in our lives.
For example, if you are on a anti-hypertensive medication,
if you're getting cancer chemotherapy,
these drugs that we take really vary
with regards to their efficacy of when they are taken.
Heart attack risks, varies as a function of time.
Inflammatory processes,
you're going to hear a little bit about inflammation.
Inflammatory processes,
how TNF, an inflammatory marker,
how TNF, tumor necrosis factor,
alters over the course of the day, or on aisle six.
These two also have rhythms.
So pain, osteoarthritic inflammatory pain,
varies as a function of day two.
And by perturbing these cycles,
we can actually perturb these biological systems,
we can have an impact on how medications
and diseases will actually express their symptoms.
So they're not just, these systems, these rhythms
are not just important for natural function,
but they're also relevant for many,
pretty much every aspect of our lives.
As I said, medications, heart disease risk,
the number, the frequency of tachycardia,
or irregular heart rhythms,
vary as a function of day.
Heart attacks are more common in the morning.
So, these systems are relevant,
they're part of our natural lives,
and we often tend not to listen to them.
And that leads to a state of sleep deprivation,
or sleep deficiency.
Sleep, by itself, is a very important biological process.
Short sleep has been associated with a higher risk
for high blood pressure, high risk of diabetes,
obviously a high risk for motor vehicle accidents,
and in the health care professional industry,
high risk for medical mistakes.
So there's a huge increasing awareness in our field
that the amount of sleep that we're getting these days,
which has chronically decreased
over the last five to seven decades,
is having a massive impact,
on not just functionality issues,
but also the fact that it actually increases our risk
for chronic medical conditions.
Beyond hypertension, beyond the risk for diabetes,
clearly our performance is impaired,
and perhaps the most important thing.
We think that we can beat the system.
We can't.
I've seen numerous articles in Time
where the cover of Time will have Sleep is for Sissies.
I don't know if you've seen that.
It's amazing that our culture,
and now, even perhaps, worse with the internet boom,
has really sort of played down the relevance of sleep
as a biological process.
The relevance of sleep is beyond some of these
functional and cardiovascular issues.
Let me tell you something that's very relevant.
If you were to graph the average amount of sleep
western societies have been getting over the last 100 years,
and in the same graph, plot the average Body Mass Index,
an index of obesity, it's gone in the inverse direction.
There's a lot of controversy about this relationship,
but what has been posed is that sleep has direct
effects on hormonal regulation of appetite.
What happens to you after a night of sleep deprivation?
What do you crave the most the next day?
Any ideas?
I'm not even gonna say it, because you've said it.
And so, the high glycemic load,
as most of you know, seems to be an important culprit.
So, sleep, the biological rhythmicity of sleep,
is relevant for a number of different issues,
not just normal performance,
but chronic medical condition risk factor,
but also our just weight.
Sleep can be interfered by artificial means.
Gotta get up at four, checking my email at 12,
one o'clock at night time, but it can also be interfered
by other medical conditions.
Conditions such as sleep apnea,
a very common thing that comes with age and weight
can also interfere with sleep quality
and lead to derangements that are associated
with poor sleep quality.
So there are two things to think about sleep.
Quality and quantity.
Both matter.
There's a third thing I would like to put in there,
which is timing.
So, quantity of sleep matters,
quality of sleep matters,
and where you get to sleep also matters.
These are the three aspects of sleep
that are relevant, again, for all biological systems.
I'm gonna end here, because I'm at 19 minutes, and counting.
I'm sure I could go on forever on this topic,
and I'm sure you will ask me many questions
about all the disorders that you face.
I'm absolutely available, and that marks my 20 minute mark.