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:
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?
Competing interests
None declared
A balance of factors
Daniel Kripke, University of California, San Diego
23 August 2007
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 [3]. 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 [5], 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 phase response.
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.
Nice paper, but I have one little question
1 August 2007
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?
Competing interests
None declared
A balance of factors
23 August 2007
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 [3]. 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 [5], 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 phase response.
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.
Competing interests
None.