Social relationships, sleep quality, and interleukin-6
in aging women
Elliot M. Friedman*†, Mary S. Hayney‡, Gayle D. Love§, Heather L. Urry¶, Melissa A. Rosenkranz¶, Richard J. Davidson¶,
Burton H. Singer†?, and Carol D. Ryff§
*Robert Wood Johnson Health & Society Scholars Program, Department of Population Health Sciences,‡School of Pharmacy,§Institute on Aging, and
¶Department of Psychology, University of Wisconsin, Madison, WI 53726; and?Office of Population Research, Princeton University, Princeton, NJ 08544
Contributed by Burton H. Singer, October 24, 2005
This study examined the interplay of social engagement, sleep
quality, and plasma levels of interleukin-6 (IL-6) in a sample of
aging women (n ? 74, aged 61–90, M age ? 73.4). Social engage-
ment was assessed by questionnaire, sleep was assessed by using
the NightCap in-home sleep monitoring system and the Pittsburgh
Sleep Quality Index, and blood samples were obtained for analysis
of plasma levels of IL-6. Regarding subjective assessment, poorer
sleep (higher scores on the Pittsburgh Sleep Quality Index) was
associated with lower positive social relations scores. Multivariate
regression analyses showed that lower levels of plasma IL-6 were
predicted by greater sleep efficiency (P < 0.001), measured objec-
tively and by more positive social relations (P < 0.05). A significant
interaction showed that women with the highest IL-6 levels were
those with both poor sleep efficiency and poor social relations (P <
0.05). However, those with low sleep efficiency but compensating
good relationships as well as women with poor relationships but
compensating high sleep efficiency had IL-6 levels comparable to
those with the protective influences of both good social ties and
for negative health outcomes. In particular, we focus on sleep
quality and its interactions with social engagement in predicting
factors because all have been linked with important health out-
comes and with aging processes. For example, IL-6, an inflamma-
tory factor whose concentration generally increases in the blood
with age (1–6), has been linked with Alzheimer’s disease, osteo-
porosis, rheumatoid arthritis, cardiovascular disease, and some
forms of cancer (1, 2, 5–7), and it is prospectively associated with
general disability (3) and mortality (8) in large population-based
poor sleep quality increases the risk of mortality (12). Low sleep
quality has also been linked to elevated IL-6 levels in patients with
clinical sleep disorders (13) and experimental studies involving
healthy volunteers (14–16). Social relationships, in addition, have
been linked with sleep quality. Whether measured objectively or
subjectively, sleep efficiency is lower and time awake during the
18). Self-reported sleep quality is also lower in married men and
women who report higher levels of attachment anxiety, an effect
that is independent of depressive affect (13). Potential links be-
tween social relationships and IL-6 are less well established, al-
though we recently reported that positive relations with others
significantly predicted lower plasma levels of IL-6 in aging
together to assess whether the optimally low IL-6 profile would be
and good sleep quality and, conversely, whether those with high
levels of IL-6 would lack both protective influences. Such inquiry
n this study, we probe an elderly population to identify social and
behavioral factors that may characterize persons at reduced risk
we were also interested in possible compensatory (interactive)
influences, for example, whether those with poor sleep quality who
nonetheless had good quality relationships and those with poor
quality relationships who had good quality sleep might also show
lower levels of IL-6. A further possibility is that sleep quality
mediates the association of social relations and plasma IL-6. Our
analyses tested for both moderating and mediating influences (20).
Such inquiry responds to the growing interest in factors that
call for integrative studies that combine influences on health across
multiple domains (psychological, social, behavioral, and biological)
(16). We tested these relationships by using self-reported and
objective sleep assessments. The NightCap system provides objec-
tive measures of sleep latency, total sleep duration, duration of
rapid eye movement (REM) and non-rapid eye movement
(NREM) stages, and sleep efficiency. Use of the NightCap system
facilitated data collection in participants’ homes, and the data
obtained previously has compared favorably to those gathered in
the laboratory (21, 22). This method was used to examine the
impact of loneliness on sleep (17). Participants also completed the
Pittsburgh Sleep Quality Index (PSQI), a measure of self-rated
sleep quality (19). Positive social engagement was operationalized
by using the positive relations with others scale, one of Ryff’s six
linked to several biological markers of health (24, 25), including
plasma IL-6 (unpublished data).
Participants. Respondents from a prior longitudinal study of aging
(see refs. 26 and 27) were contacted by mail and invited to
participate in an additional study involving biomarker data collec-
tion, and volunteers were enrolled until a target number of 135 was
reached. There were no inclusion or exclusion criteria, except the
ability and willingness to travel to the General Clinical Research
Center (GCRC) on the University of Wisconsin, Madison campus
for an overnight stay. Consent for all procedures was obtained
during the GCRC visit. Among those who did not participate, 16%
were ineligible (because of death, severe morbidity, or moving out
of difficulties with travel or for reasons of health). However, this
newly recruited biomarker sample of 135 participants was not
significantly different from the original longitudinal sample with
regard to health (chronic conditions and health symptoms), in-
come, and marital status, but was significantly younger and had
more education. The biomarker sample ranged in age from 61 to
Conflict of interest statement: No conflicts declared.
Freely available online through the PNAS open access option.
Abbreviations: GCRC, General Clinical Research Center; HPA, hypothalamic–pituitary–
†To whom correspondence may be addressed. E-mail: firstname.lastname@example.org or singer@
© 2005 by The National Academy of Sciences of the USA
December 20, 2005 ?
vol. 102 ?
no. 51 ?
relations scores, or plasma IL-6 levels were highly fluctuating,
time-dependent domains, it would reduce the likelihood of observ-
ing significant relationships among them. As such, the data we had
available translated to a relatively conservative test of our hypoth-
eses, and the results suggest, in part because of the temporal
Increased variability in psychological and biological functioning
with age is a key issue undergirding this study. Most research,
however, has focused on changes in average levels of function.
Increases in IL-6 that typically occur with age, for example, are
linked to increased risk of disease, disability, and mortality (1–3,
6–8, 59–62). As a consequence, less attention has been paid to the
variance in markers of aging (15). The results of this study indicate
that although poor social relationships and poor sleep quality
scores on either variable also compensate for the presence of low
those in women with both strong social relationships and high
quality sleep. Thus, these findings suggest that strong social rela-
tionships and good quality sleep contribute, additively and inter-
actively, to advantaged biological profiles in aging women. They
also offer a potential target for interventions designed to increase
given the steadily rising proportion of older adults in western
countries, particularly the United States.
This research was supported by the Robert Wood Johnson Foundation,
National Institute on Aging Grant P01-AG020166, National Institute of
Mental Health Grant P50-MH61083, and National Institutes of Health
Grant M01-RR03186 (to GCRC, University of Wisconsin).
1. Ershler, W. B. (1993) J. Am. Geriatr. Soc. 41, 176–181.
2. Ershler, W. B. & Keller, E. T. (2000) Annu. Rev. Med. 51, 245–270.
3. Ferrucci, L., Harris, T. B., Guralnik, J. M., Tracy, R. P., Corti, M. C., Cohen, H. J.,
Penninx, B., Pahor, M., Wallace, R. & Havlik, R. J. (1999) J. Am. Geriatr. Soc. 47,
4. Kiecolt-Glaser, J. K., Preacher, K. J., MacCallum, R. C., Atkinson, C., Malarkey,
W. B. & Glaser, R. (2003) Proc. Natl. Acad. Sci. USA 100, 9090–9095.
5. Krabbe, K. S., Pedersen, M. & Bruunsgaard, H. (2004) Exp. Gerontol. 39, 687–699.
6. Papanicolaou, D. A., Wilder, R. L., Manolagas, S. C. & Chrousos, G. P. (1998) Ann.
Intern. Med. 128, 127–137.
T. B. (2001) Circulation 103, 947–953.
8. Harris, T. B., Ferrucci, L., Tracy, R. P., Corti, M. C., Wacholder, S., Ettinger, W. H.,
Jr., Heimovitz, H., Cohen, H. J. & Wallace, R. (1999) Am. J. Med. 106, 506–512.
9. Yoon, I. Y., Kripke, D. F., Elliott, J. A., Youngstedt, S. D., Rex, K. M. & Hauger,
R. L. (2003) J. Am. Geriatr. Soc. 51, 1085–1091.
10. Foley, D. J., Monjan, A. A., Brown, S. L., Simonsick, E. M., Wallace, R. B. & Blazer,
D. G. (1995) Sleep 18, 425–432.
11. Ohayon, M. M., Carskadon, M. A., Guilleminault, C. & Vitiello, M. V. (2004) Sleep
12. Dew, M. A., Hoch, C. C., Buysse, D. J., Monk, T. H., Begley, A. E., Houck, P. R.,
Hall, M., Kupfer, D. J. & Reynolds, C. F., 3rd. (2003) Psychosom. Med. 65, 63–73.
13. Carmichael, C. L. & Reis, H. T. (2005) Health Psychol. 24, 526–531.
14. Lupien, S. J. & Wan, N. (2004) Philos. Trans. R. Soc. London B 359, 1413–1426.
15. Rowe, J. W. & Kahn, R. L. (1987) Science 237, 143–149.
16. Singer, B. H. & Ryff, C. D. (2001) New Horizons in Health: An Integrative Approach
(Natl. Acad. Press, Washington, DC).
17. Cacioppo, J. T., Hawkley, L. C., Berntson, G. G., Ernst, J. M., Gibbs, A. C., Stickgold,
R. & Hobson, J. A. (2002) Psychol. Sci. 13, 384–387.
18. Cacioppo, J. T., Hawkley, L. C., Crawford, L. E., Ernst, J. M., Burleson, M. H.,
Kowalewski, R. B., Malarkey, W. B., Van Cauter, E. & Berntson, G. G. (2002)
Psychosom. Med. 64, 407–417.
19. Buysse, D. J., Reynolds, C. F., 3rd, Monk, T. H., Berman, S. R. & Kupfer, D. J. (1989)
Psychiatry Res. 28, 193–213.
20. Marks, N. F., Lambert, J. D. & Choi, H. (2002) J. Marriage Fam. 64, 657–667.
21. Cantero, J. L., Atienza, M., Stickgold, R. & Hobson, J. A. (2002) Sleep 25, 238–245.
23. Ryff, C. D. & Keyes, C. L. (1995) J. Pers. Soc. Psychol. 69, 719–727.
23. Ryff, C. D. & Singer, B. (2000) Pers. Soc. Psychol. Rev. 4, 30–44.
25. Ryff, C. D., Love, G. D., Muller, D., Urry, H., Friedman, E. M., Davidson, R. J. &
Singer, B. Psychother Psychosom., in press.
26. Kling, K. C., Ryff, C. D. & Essex, M. J. (1997) Pers. Soc. Psychol. Bull. 23, 981–990.
27. Kwan, C. M., Love, G. D., Ryff, C. D. & Essex, M. J. (2003) Psychol. Aging 18, 3–12.
28. Keyes, C. L. M., Shmotkin, D. & Ryff, C. D. (2002) J. Pers. Soc. Psychol. 82,
29. Ryff, C. D., Singer, B. H. & Love, G. (2004) Philos. Trans. R. Soc. London B 359,
30. Ryff, C. D. (1989) J. Pers. Soc. Psychol. 57, 1069–1081.
31. Helmersson, J., Larsson, A., Vessby, B. & Basu, S. (2005) Atherosclerosis 181,
32. Volpato, S., Pahor, M., Ferrucci, L., Simonsick, E. M., Guralnik, J. M., Kritchevsky,
S. B., Fellin, R. & Harris, T. B. (2004) Circulation 109, 607–612.
33. Riedel, B. W., Durrence, H. H., Lichstein, K. L., Taylor, D. J. & Bush, A. J. (2004)
Behav. Sleep Med. 2, 63–78.
34. Roehrs, T. & Roth, T. (2001) Alcohol Res. Health 25, 101–109.
35. You, T., Yang, R., Lyles, M. F., Gong, D. & Nicklas, B. J. (2005) Am. J. Physiol.
Endocrinol. Metab. 288, E741–E747.
36. Yudkin, J. S., Kumari, M., Humphries, S. E. & Mohamed-Ali, V. (2000) Atheroscle-
rosis 148, 209–214.
37. Aiken, L. S. & West, S. G. (1991) Multiple Regression: Testing and Interpreting
Interactions (Sage Publications, Thousand Oaks, CA).
38. Vgontzas, A. N., Zoumakis, M., Bixler, E. O., Lin, H. M., Prolo, P., Vela-Bueno, A.,
Kales, A. & Chrousos, G. P. (2003) J. Clin. Endocrinol. Metab. 88, 2087–2095.
39. Vgontzas, A. N., Papanicolaou, D. A., Bixler, E. O., Lotsikas, A., Zachman, K., Kales,
A., Prolo, P., Wong, M. L., Licinio, J., Gold, P. W., et al. (1999) J. Clin. Endocrinol.
Metab. 84, 2603–2607.
41. Irwin, M., Rinetti, G., Redwine, L., Motivala, S., Dang, J. & Ehlers, C. (2004) Brain
Behav. Immun. 18, 349–360.
42. Hong, S., Mills, P. J., Loredo, J. S., Adler, K. A. & Dimsdale, J. E. (2005) Brain Behav.
Immun. 19, 165–172.
43. Crowther, M. R., Parker, M. W., Achenbaum, W. A., Larimore, W. L. & Koenig,
H. G. (2002) Gerontologist 42, 613–620.
44. Rowe, J. W. & Kahn, R. L. (1998) Successful Aging (Pantheon?Random House, New
45. Spath-Schwalbe, E., Gofferje, M., Kern, W., Born, J. & Fehm, H. L. (1991) Biol.
Psychiatry 29, 575–584.
46. Van Cauter, E., Leproult, R. & Plat, L. (2000) J. Am. Med. Assoc. 284, 861–868.
47. Van Cauter, E., Leproult, R. & Kupfer, D. J. (1996) J. Clin. Endocrinol. Metab. 81,
48. McEwen, B. S. (2000) Neurochem. Res. 25, 1219–1231.
49. Plotsky, P. M., Owens, M. J. & Nemeroff, C. B. (1998) Psychiatr. Clin. North Am. 21,
50. Zorrilla, E. P., Luborsky, L., McKay, J. R., Rosenthal, R., Houldin, A., Tax, A.,
McCorkle, R., Seligman, D. A. & Schmidt, K. (2001) Brain Behav. Immun. 15,
51. Miller, G. E., Cohen, S. & Ritchey, A. K. (2002) Health Psychol. 21, 531–541.
52. Urry, H. L., Nitschke, J. B., Dolski, I., Jackson, D. C., Dalton, K. M., Mueller, C. J.,
Rosenkranz, M. A., Ryff, C. D., Singer, B. H. & Davidson, R. J. (2004) Psychol. Sci.
53. Bauer, J., Hohagen, F., Ebert, T., Timmer, J., Ganter, U., Krieger, S., Lis, S., Postler,
E., Voderholzer, U. & Berger, M. (1994) Clin. Invest. 72, 315.
54. Irwin, M. (2002) Brain Behav. Immun. 16, 503–512.
55. Morrow, J. D. & Opp, M. R. (2005) Brain Behav. Immun. 19, 28–39.
56. Roberts, R. E., Shema, S. J. & Kaplan, G. A. (1999) Psychosom. Med. 61, 188–196.
57. Kryger, M., Monjan, A., Bliwise, D. & Ancoli-Israel, S. (2004) Geriatrics 59, 24–30.
58. Bryant, P. A., Trinder, J. & Curtis, N. (2004) Nat. Rev. Immunol. 4, 457–467.
59. Cesari, M., Penninx, B. W., Newman, A. B., Kritchevsky, S. B., Nicklas, B. J.,
Sutton-Tyrrell, K., Tracy, R. P., Rubin, S. M., Harris, T. B., Pahor, M., et al. (2003)
Am. J. Cardiol. 92, 522–528.
61. Roubenoff, R., Parise, H., Payette, H. A., Abad, L. W., D’Agostino, R., Jacques, P. F.,
Wilson, P. W., Dinarello, C. A., Harris, T. B., Penninx, B. W., et al. (2003) Am. J. Med.
62. Vasan, R. S., Sullivan, L. M., Roubenoff, R., Dinarello, C. A., Harris, T., Benjamin,
E. J., Sawyer, D. B., Levy, D., Wilson, P. W. & D’Agostino, R. B. (2003) Circulation
www.pnas.org?cgi?doi?10.1073?pnas.0509281102Friedman et al.