Daniel F Kripke*, Jeffrey A Elliott, Shawn D Youngstedt and Katharine M Rex
Corresponding author: Daniel F Kripke DKripke@ucsd.edu
Journal of Circadian Rhythms 2007, 5:4 doi:10.1186/1740-3391-5-4
(2007-08-23 01:16) University of California, San Diego
Dr. Zivkovic is absolutely right that we might expect the circadian oscillators of
older adults to be weaker, and for that reason, easier to phase shift. That is, weaker
amplitude in overt circadian rhythms could reflect a lower amplitude central pacemaker
leading theoretically to higher-amplitude phase-response curves [1-2]. One indication
that older people have weaker oscillators is the lower overt amplitude of many rhythms
such as body temperature, activity, and melatonin. Another indication may be the
longer duration of melatonin secretion observed, as this may be analogous to increased
melatonin duration and activity time (α) in nocturnal rodents . Increased
duration of nocturnal wheel-running in hamsters corresponds to a circadian pacemaker
which is easier to shift [4,5], and therefore might possibly have a lower functional
amplitude. Emerging evidence suggests that increased activity duration (α) may
correspond to the dispersion of the phases of the circadian rhythms of individual
pacemaker neurons within the suprachiasmatic nucleus. The more dispersed the phases,
the weaker the compound oscillator resulting from coupling of these neurons would
be. Nonetheless, if decreased pacemaker amplitude contributes importantly to the increased
amplitude of light induced phase shifts typical of hamsters exposed to short-photoperiods,
oscillator theory predicts that the lower amplitude circadian pacemaker will also
show more robust phase shifts to other phase shifting stimuli. However, this expectation
was not confirmed for the case for novel wheel-running induced shifts , indicating
that these relationships warrant further research.
From a different perspective, we expected older adults to have more yellowing of the
ocular lens and poorer transmission of the blue-green wave lengths most important
in producing phase shifts. Retinal deterioration associated with aging could be another
factor. Thus with aging, poorer transmission of the light signal to the retina and
from there to the suprachiasmatic nucleii would perhaps tend to produce a weakened
It would appear that in the particular older adult sample that we studied, the above
factors favoring strong phase shifts and those favoring weaker phase shifts were roughly
balanced or not as important as suggested above. However, among adults of greater
age or poorer health status, the balance might be different.
Regarding the other question, we did not plan to provide all the results for temperature,
cortisol, and activity, since as far as we could see, they were entirely consistent
with results for aMT6s but merely less statistically significant (for the most part).
We have not discerned any reliable differences between variables in the phase responses.
To present those data in detail would raise more statistical questions (since several
P values were >0.05 or marginal) which might be difficult to resolve or explain.
Daniel F. Kripke, M.D.
Jeffrey A. Elliott, Ph.D.
1. Johnson CH, Elliott JA, Foster R, Honma K-I, Kronauer R: Fundamental properties
of circadian rhythms. In: Chronobiology: Biological Timekeeping. Edited by Dunlap
JD, Loros JJ, DeCoursey PJ. Sunderland, MA: Sinauer Associates, Inc. 2004:67-105.
2. Johnson CH, Elliott JA, Foster R: Entrainment of circadian programs. Chronobiology
Intl. 2003, 20:741-744.
3. Elliott JA and Tamarkin L: Complex circadian regulation of pineal melatonin and
wheel running in Syrian hamsters. . Comp Physiol A 1994, 174:469 484.
4. Pittendrigh CS, Elliott JA, and Takamura T: The circadian component in photoperiodic
induction. (CIBA. Foundation. Symposium 104). , 1984: 26 47.
5. Evans JA, Elliott JA, Gorman MR: Photoperiod differentially modulates photic and
nonphotic phase response curves of hamsters. Am J Physiol 2004, 286:R539-46.
(2007-08-01 02:15) PLoS
This work is well thought-out and well done. I do not think that the negative result
(i.e., no difference between young and old) is a reason to despair - I find it quite
informative. I have explained in more detail here:
The Amplitude Problem
Will all the data (e.g., temperature PRC, etc.) be available as Supplementary Information?
Finally, is it a mistake that you expected a smaller sizes of phase-shifts in a lower-amplitude
system? Shouldn't you expect greater shifts when the amplitude is lower?
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