Dr. Jayant Biswas

1. CHRONOBIOLOGICAL CONCEPT : TO DEAL WITH MODERN LIFESTYLE Dr. Jayant Biswas

2. What are body rhythms? • Body rhythms are biological processes that show cyclical variation over time…ranging from hours to years and reflect the influence of the earths rotation upon us… it's living inhabitants, along with plants and animals.

3. Glossary of Chronobiological Terms • Biological clock; a term implying an underlying/internal physiological mechanism that gives a time sense to every living organisms i.e., when to eat, sleep/awake etc. • Biological rhythm; a cyclical, repeated variation in a biological function. • Circadian rhythm; a cyclical variation in a metabolic , physiological or behvioural process with a period of about 24h when in constant conditions (the term ‘circadian’ is derived from the Latin circa meaning about and diem meaning day). • Ultraradian: Rhythms faster than 24 h • Infradian: Rhythms slower than 24 h • Circaseptan rhythm; a cyclical variation in a metabolic, physiological or behvioural process with a period of about a week when in constant conditions. • Circannual rhythm; a cyclical variation in a metabolic, physiological or behvioural process with a period of about an year.

4. Glossary of Chronobiological Terms • Crepuscular activity; an activity mainly performed at dusk and/or dawn. • Critical photoperiod;that 24h LD ratio at which 50% of the population under study is photoperiodically switched from one state to another, e.g. into flowering from non-flowering, or into development from diapause. • Diapause; a period of arrested growth or reduced physiological activity, commonly induced by a seasonal change in photoperiod (i.e. day-length); a term used mainly for invertebrates, especially insects. • Diel rhythm; a rhythm that has been measured only in natural or artificial day-night cycles, and not yet known to persist in constant conditions – cf. circadian. • Diurnal activity; activity performed mainly during the daytime – cf. Nocturnal. • Dormancy; a term used either more or less synonymously with diapause, but especially for plants.

5. Glossary of Chronobiological Terms • Endogenous; of rhythms or other forms of biological timekeeping controlled from within the organism by some kind of physiological ‘ biological clock ’. • Entrainment; the synchronization of one biological rhythm to another or to a zeitgeber cycle, e.g. circadian rhythm are often entrained to the light-dark cycle. • Exogenous;of rhythms or other biological timekeeping that arise solely, or mainly, as direct responses to environmental signals cf. Endogenous. • Free-running;when biological rhythms run at their own ‘natural’ frequency in constant conditions, and which are therefore not entrained to a zeitgeber such as a day-night cycle and so are only generated and controlled by the biological clock. • Hibernation;winter or cold season dormancy. • Hour-glass; an interval-timer which does not oscillate (i.e. repeat its timing cycle) in constant conditions.

6. Glossary of Chronobiological Terms • Melatonin; a hormone produced rhythmically in vertebrates by the pineal gland, a pea sized organ at the center of the human brain. • Nocturnal activity; activity performed mainly at night – cf. Diurnal. • Oscillator; the internal and therefore unseen, or endogenous oscillator (the biological clock ) that produces an overt measurable biological rhythm in the organism. • Period; the length of one complete cycle of a rhythm. • Phase; a particular reference point in the cycle of a rhythm, e.g. the daily onset of locomotor activity, or the light-to-dark transition in a zeitgeber cycle. • Phase-response curve (orPRC); the 24h profile of an organism’s phase shifts in response to environmental signals. • Phase shift;a shift in a biological rhythm along its time axis so whilst the period remains the same the time at which the rhythm occurs changes e.g. a rhythm normally occuring at 2pm experiences a 2 hour phase shift and so then starts at 4pm instead. The term phase shift is also used to mean theresetting of a rhythm; either as an advance shift (i.e.earlier ), or as a delay shift (i.e. later ) along the rhythms time axis.

7. Glossary of Chronobiological Terms • Photoperiodism;the seasonal day-length responses that cause altered physiological states such as flowering or non-flowering, diapause or development; the photoperiod is usually taken as the time between lights-on and lights-out in an artificial LD cycle (though many photoperiodic responses are in reality to changes in night length) – see critical photoperiod . • Rhythm; a function which oscillates or cycles at a regular frequency. Biological rhythms are the overt, measurable activities generated by some internal oscillator (or ‘clock’). • Skeleton photoperiod; experimental photoperiod cycle consisting of one long light phase followed by darkness interrupted by a short light break, with the organism responding as if the interval between the first light-on and the second light-off marked a single photophase. • Tau; The ‘natural’ period of a biological rhythm free-running in constant conditions. • Temperature coefficient. • Temperature compensation; In simple terms Biological Clocks are not effected by different temperatures, whereas other physiological systems are.

8. Glossary of Chronobiological Terms • Zeitgeber; from the German for meaning "time giver". A periodic environmental signal that entrains some biological rhythm , for example a natural or artificial day-night cycle for a circadian rhythm ( but may also be a temperature cycle, or social cycle). • Zeitgedächtnis; from the German for ‘time-memory’. Used mainly in reference to the time-sense in honey bees by which they can be trained to come to feed at particular times of day.

9. Examples of Biological Rhythms • Seasonal migrations • Mating seasons • Menstruation • Circadian rhythms: • Daily rhythms

10. Inherent Biological Rhythms • Biosystems Rhythms • second cycles (sec) - cardiac • circadian (day) - sleep cycle - melatonin (pineal) • circaseptan (week) - mitotic activity of human bone marrow, balneology, bilirubin cycle neonatology • circalunar cycles (month) - menstrual cycle • annual (year) cycles - animal’s coats – weight loss & gain by the season.

11. Zeitgebers: External Cues Help Set Circadian Rhythms • Internal clocks interact with zeitgebers. • Light is an important human zeitgeber. • Human “free-running” cycle is about 25 hours. • Blind individuals and sailors serving on submarines may experience sleep problems.

12. Synchronizers • Light information transmitted to the brain by non-visual neurons originating in the back of the eye • stimulated by light, temperature social interactions, barometric pressure etc. etc.

13. The Suprachiasmatic Nucleus in the Body’s Master Internal Clock • “supra” – above (above optic chiasm) • SCN is near: • Hypothalamus • Flow of visual info • Retinohypothalamic pathway • Axons from eyes going to hypothalamus • Provides light info to hypothalamus to maintain circadian rhythms

14. SCN Activity and Light/Dark Cycles • The SCN is activeduring the day in both diurnal and nocturnal animals. • The SCN tells the animal whether it’s day or night, but not how to behave. • Transplants of SCN establish donor rhythms in recipient animals.

15. Single SCN explants generate a circadian rhythm Reppert, S.M. & Weaver, D.R., Nature 418, 935 - 941 (2002)

16. How the Internal Clock works • Oscillations of protein production and degradation serves as the “ticking” of the internal clock (takes about 24 hours). • Light may participate in the triggering of some of these protein fluctuations.

17. The Biochemistry of Circadian Rhythms • Cortisol • release is highest in the morning and drops during the day. • Glutamate • Released by the retinohypothalamic tract during light • Melatonin • released only at night (by the retina and the pineal gland).

18. Is the biological clock really a clock?A Comparison • Wrist watch • Driven with a pre-determined period (nearly 24h) • Has error • Able to re-set • “Free will” • We act in accordance or defiance of the clock • Can give to others • SCN (biological clock) • Driven by a genetic program with a pre-determined period (~24.1h) • Has error • Able to re-set • “Free will” • We act in accordance or defiance of the clock • Can give to others

19. Viewpoint Challenge • Traditional view – biological rhythms are exogenous • Blood pressure variation is interpreted as an activity variation, thus external. • Now, many claim that biological rhythms are endogenous • Blood pressure variation is interpreted as a hormonal variation, thus internal.

20. The consequences of disrupting Biological rhythms. • When external cues change we have to re-adjust our internal clock……. SHIFT WORK JET LAG

21. What is Shift Work? • The term shift work is defined as an arrangement of work hours that uses two or more teams (shifts) of workers in order to extend the hours of operation of the work environment, beyond that of the conventional office hours. • Knutsson, 1989

22. Why population of shift workers increasing day by day? • We need doctors, nurses, policeman, hotel staff etc. as a part of our social life. • Expensive machines and continuity in their functioning in modern industries is extremely mandatory and cost-effective. • Quality in the current-day lifestyle demands immediate and round-the-clock service from various indispensable sectors.

23. Problems with shift Work • Rising early or retiring to bed earlier than normal is an example of phase advance. • Going to bed late or getting up late is an example of phase delay. • By delaying/advancing our rhythms we are compromising our ability to cope in the short term. • On average it takes approx 3 days to adjust to a 12 hour shift in time.

24. Exposure to Shift Work with Circadian Disruption Involves: • Internal & External Desynchronization • Exposure to Light at Night (LAN, “Light Toxicity”) with Suppression of Melatonin • Sleep Deprivation with: • Neuro- Endocrine Changes, • Immune- Suppression. • Increased sleepiness: Poor sleep, both qualitative and quantitative.

25. Major Problem: Performance decrement • Besides several Psychosocial/ Psychophysiological/ Clinical Problems, the most dangerous is the decrement in overall performances of the Shift-workers. • Shift workers are more susceptible to diminished performance and attention deficits that considerably compromise public health safety and productivity. • Safety declines over successive • night shifts (Folkard & Tucker 2003).

26. Major Accidents due to Negligency during Shift Work • Tragedy Time • Bhopal gas tragedy 00.56 h • Chernobyl nuclear disaster 01.23 h • Three-mile Island incident 04.00 h • Rhine chemical spillage Early morning • Gaisal train disaster 01.15 h • In the US $77billion annually as a result of accidents and ongoing medical expenses due to shift work related illnesses.

27. How can we lessen the impact/effects of shift work? • Select the Morning type and Evening type of people and distribute the shit accordingly Chronotype OWL Type LARK Type

28. How can we lessen the impact/effects of shift work? • Speed Rotation: • Fast Vs Slow • Direction of Rotation: • Clockwise Vs. Anticlockwise

29. How can we lessen the impact/effects of shift work? • Clockwise rotation: • Better tolerated by the shift workers • Improve production & well-being (Czeisler et al., 1982) • Improve sleep quality (Folkard 1993) • Reduce physical, social and psychological problems (Landén 1981) • Quickly rotating shift system: • Minimize sleep deprivation (Fischer et al., 1997) • Minimize circadian rhythm disruption (Knauth 1993, 1995) • Improve social contacts (Knauth 1993, 1995) • Improve alertness and well-being (Williamson & Sanderson 1986, Phillips et al., 1991)

30. JET LAG Jet Lag does not occur form North-South and vice versa!! Jet Lag only occurs when flying from East-West or from West to East. In other words when we change time zones. Example You fly from Scotland –Boston (USA). You leave at 11am arrive 5pm British time actually it is 12pm in Boston...by 8pm Boston time you’ll be tired as it is 1am to you normally!!

31. JET LAG • Its easier to adapt to jet lag when flying in a westerly direction because the day of travel is lengthen, whereas it is shortened when travelling east! • As our endogenous cycle is about 25 hours we are more able to cope with phase delay than phase advance. • We can stay up when we should be a sleep but we don’t like being woken we want to sleep!

32. JET LAG • Evidence Schwartz et al (1995) found that east coast US baseball teams did better when travelling West (phase delay) than West coast teams who travelled East (phase advance). The time difference was 3 hours. This would give the East coast an advantage!!

33. Jet Lag…How can we lessen the impact/effects of Jet Lag? • Use melatonin to reset the body clock.. • Adopt local eating times etc to help reset the biological clock as soon as possible.

36. Application of chronobiology across the lifespan:Adolescence • 15 year old student with difficulty waking up in the morning, finds his best “study time” is between 9 pm and 1 am and hasn’t gone to sleep before 2 am for the past 4 weeks. • What is this? What can he do about it? • A 65 year old man retired from a career in finance wants to watch the late show with his wife and sleep-in now that he’s retired, but he feels compelled to sleep at 8:30 pm and is awake each morning at 4 am. Wife is offended that he’s “avoiding” her at night. • What is this? What can he do about it?

37. Mental Tiredness

38. Sleeplessness

39. Insomnia

40. Sleeping Inertia

41. THANK YOU FOR YOUR PATIENCE