“Two Are Better Than One”: Loneliness and Mortality

The Preacher sets up this saying with a portrait that should make any working man uncomfortable. “There was a certain man without a dependent, having neither a son nor a brother, yet there was no end to all his labor.” Then the man finally asks, “For whom am I laboring and depriving myself of pleasure?” (Ecclesiastes 4:8). The verses on companionship answer that lonely, driven man. The answer is practical: a partner who lifts you when you fall, warmth on a cold night, and help against an attacker. The “cord of three strands” in verse 12 most naturally means that each companion added makes the bond stronger. Christians have long heard God as the third strand. That reading is a fair application, but it is not the verse’s plain sense.

This observation has some of the strongest empirical backing of anything in this paper. Holt-Lunstad, Smith, and Layton (2010) meta-analyzed 148 prospective studies covering 308,849 participants. People with stronger social relationships had about 50% greater odds of surviving the follow-up periods (odds ratio 1.50). The effect held across age, sex, initial health status, and cause of death. It was strongest for complex measures of social integration (odds ratio 1.91). It was weakest, and not statistically significant, for simply living with someone (odds ratio 1.19). A follow-up meta-analysis separated the pieces (Holt-Lunstad et al., 2015). Being objectively isolated, feeling lonely, and living alone each carried roughly 26% to 32% greater odds of death after controlling for other factors. Objective and subjective isolation did not differ. The associations were stronger in samples younger than 65, so this is not only an old man’s problem. The most recent synthesis, 90 cohort studies with over 2.2 million people, found a smaller but still clear signal. Social isolation was linked to 32% higher risk of death from any cause and loneliness to 14% higher risk (Wang et al., 2023). A separate meta-analysis linked poor social relationships to about 29% greater risk of coronary heart disease and 32% greater risk of stroke (Valtorta et al., 2016). In 2023 the U.S. Surgeon General issued a national advisory. It noted that roughly half of American adults report loneliness and called disconnection a public health crisis (Office of the U.S. Surgeon General, 2023).

How could loneliness get under the skin? The leading account, developed by John Cacioppo and Louise Hawkley, treats loneliness as a biological alarm signal, much like hunger or thirst. For a social species, being cut off from the group used to mean danger. So the lonely brain shifts into a self-protective mode. It scans more for social threat, reads ambiguous faces and comments more negatively, sleeps more lightly, and holds back from the very people it needs (Hawkley & Cacioppo, 2010). In a small fMRI study, lonely young adults showed weaker activity in the ventral striatum, a reward hub, when viewing pleasant pictures of people rather than objects. They also showed more visual-cortex attention to other people’s distress (Cacioppo et al., 2009). In other words, the lonely brain finds people less rewarding and more threatening. That is a vicious circle, and it is exactly the man in Ecclesiastes 4:8.

That vigilance seems to reach the immune system. Steve Cole and colleagues looked at gene expression in white blood cells. In chronically lonely people they found more activity in genes that drive inflammation (via the transcription factor NF-κB). They also found less activity in genes that respond to cortisol’s anti-inflammatory signal and in genes for antiviral defense (Cole et al., 2007). Cole calls this pattern the “conserved transcriptional response to adversity.” The 2007 study compared only 14 people, so it was a first look. A larger follow-up tracked 141 older adults over time. It found that loneliness was linked to heightened sympathetic (“fight or flight”) nervous system activity and to an expansion of inflammatory monocytes, a type of immune cell. Experiments in rhesus monkeys showed the same pattern, along with cells that had become less sensitive to cortisol and a weaker antiviral response (Cole et al., 2015). Put simply, the body of a chronically isolated person behaves as if it expects wounds. It readies for inflammation at the cost of fighting viruses. Over years, chronic low-grade inflammation is linked to heart disease and other illnesses. An honest limit: a meta-analysis of blood inflammatory markers found mixed results. Loneliness was linked to interleukin-6 only in the most-adjusted analyses, and not to C-reactive protein. Isolation was linked most consistently to fibrinogen (K. J. Smith et al., 2020). The pathway is plausible and partly supported, not settled. Health behaviors such as smoking, drinking, inactivity, and skipped doctor visits almost certainly add to it.

Rejection also registers in the brain as distress. In a well-known small study, people who were left out of a virtual ball-tossing game showed more activity in the dorsal anterior cingulate cortex, a region also active in physical pain, and that activity tracked how distressed they felt (Eisenberger et al., 2003). Later work using more refined pattern analysis in 60 people found that the brain’s representations of physical pain and of rejection overlap in location but are distinct (Woo et al., 2014). So “rejection literally hurts like a burn” overstates the finding. What holds up is more modest: social disconnection engages the brain’s distress and threat systems.

Where does the church come in? Several large Harvard cohort studies have tracked religious service attendance. In the Nurses’ Health Study, women who attended more than once a week had 33% lower all-cause mortality over about 16 years than women who never attended. That study covered 74,534 women and 13,537 deaths (hazard ratio 0.67; Li et al., 2016). Social support explained about 23% of that association. In a second analysis of 89,708 women in the same cohort, weekly attendance was linked to a roughly five-fold lower suicide rate (VanderWeele et al., 2016). Across three U.S. cohorts that included men, weekly attenders had 26% lower mortality and less depression, hopelessness, and loneliness (Chen et al., 2021). The limits are real. These studies are observational, the strongest data come from women who were nurses, and people who attend may differ in ways no model fully captures. But the pattern is consistent: sharing life with a worshiping community travels with longer, less lonely lives.

That last detail matters for men. Sharing an address is not the same as being known. In a 2021 national survey, 15% of men reported having no close friends. That is up from 3% of all adults in a 1990 Gallup poll, though the two surveys used different methods. Only 21% of men had received emotional support from a friend in the past week, compared with 41% of women (Cox, 2021). The data favor rich, multi-stranded integration, the kind of “cord of three strands” a committed small group can provide.

Practice

Living it out

Five practices drawn from this passage. Each says how strong the research behind it is. What the labels mean.

1. 1

   Name your “lifter” and tell him

   Verse 10 assumes a specific person who will lift you up. Pick one or two men in this group and agree to call each other when one of you falls, whether that is a temptation, a diagnosis, or a job loss.

   See noteThe mortality link is strongest for complex, real integration (OR 1.91) and weakest for merely living near people (Holt-Lunstad et al., 2010). This is strong, consistent observational evidence, but it is not proof that adding one friend will extend your life.
2. 2

   Make the weekly empathy call

   Call a man who is homebound, widowed, recently divorced, or new to the church, and mostly listen.

   See noteIn a randomized trial with 240 adults, briefly trained young volunteers made empathy-focused phone calls over four weeks. Loneliness dropped (Cohen’s d about 0.48), and so did depression and anxiety, compared with controls (Kahlon et al., 2021). This is good evidence because it was randomized. But it was short, most participants were women, and the trial measured how people felt, not their health or survival.
3. 3

   Challenge the lonely brain’s story

   When you notice yourself thinking “nobody wants me there” or “they’re judging me,” treat it as a symptom of the alarm and not as a fact. Show up anyway, and ask a brother to check your read of the situation.

   See noteIn randomized trials, the loneliness interventions that worked best targeted these distorted social thoughts, more than simply adding social contact (Masi et al., 2011). The underlying vigilance is well described (Hawkley & Cacioppo, 2010). The evidence is moderate: the effects are real but modest.
4. 4

   Keep the weekly rhythm of worship and small group

   Treat Sunday worship and this group as fixed appointments, not leftover time.

   See noteWeekly attendance is consistently linked to lower mortality, lower suicide, and less loneliness in large prospective cohorts (Li et al., 2016; VanderWeele et al., 2016; Chen et al., 2021). This is strong observational evidence, but not experimental, and much of it comes from women. Attend for Christ’s sake. The health finding is a side effect, not the reason.
5. 5

   Use your hands as well as your words

   Put a hand on a brother’s shoulder when you pray for him, and hold your wife’s hand when she is anxious.

   See noteIn 16 married women under threat of shock, holding their husband’s hand dampened activity in threat-responsive brain regions, and the better the marriage, the bigger the effect. A stranger’s hand helped less (Coan et al., 2006). A larger follow-up with 110 adults, 59 of them men, found the same effect for spouses, partners, and close friends, but none for strangers (Coan et al., 2017; see Section 11). These studies measured brain activity, not cortisol. Moderate, and it works best with people you trust.

Studies cited on this page20

1. ↗ Cacioppo, J. T., Norris, C. J., Decety, J., Monteleone, G., & Nusbaum, H. (2009). In the eye of the beholder: Individual differences in perceived social isolation predict regional brain activation to social stimuli. Journal of Cognitive Neuroscience, 21(1), 83-92. https://doi.org/10.1162/jocn.2009.21007
2. ↗ Chen, Y., Kim, E. S., & VanderWeele, T. J. (2021). Religious-service attendance and subsequent health and well-being throughout adulthood: Evidence from three prospective cohorts. International Journal of Epidemiology, 49(6), 2030-2040. https://doi.org/10.1093/ije/dyaa120
3. ↗ Coan, J. A., Beckes, L., Gonzalez, M. Z., Maresh, E. L., Brown, C. L., & Hasselmo, K. (2017). Relationship status and perceived support in the social regulation of neural responses to threat. Social Cognitive and Affective Neuroscience, 12(10), 1574–1583. https://doi.org/10.1093/scan/nsx091
4. ↗ Coan, J. A., Schaefer, H. S., & Davidson, R. J. (2006). Lending a hand: Social regulation of the neural response to threat. Psychological Science, 17(12), 1032–1039. https://doi.org/10.1111/j.1467-9280.2006.01832.x
5. ↗ Cole, S. W., Capitanio, J. P., Chun, K., Arevalo, J. M. G., Ma, J., & Cacioppo, J. T. (2015). Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation. Proceedings of the National Academy of Sciences, 112(49), 15142-15147. https://doi.org/10.1073/pnas.1514249112
6. ↗ Cole, S. W., Hawkley, L. C., Arevalo, J. M., Sung, C. Y., Rose, R. M., & Cacioppo, J. T. (2007). Social regulation of gene expression in human leukocytes. Genome Biology, 8(9), R189. https://doi.org/10.1186/gb-2007-8-9-r189
7. ↗ Cox, D. A. (2021). The state of American friendship: Change, challenges, and loss. Survey Center on American Life. https://www.americansurveycenter.org/research/the-state-of-american-friendship/
8. ↗ Eisenberger, N. I., Lieberman, M. D., & Williams, K. D. (2003). Does rejection hurt? An fMRI study of social exclusion. Science, 302(5643), 290-292. https://doi.org/10.1126/science.1089134
9. ↗ Hawkley, L. C., & Cacioppo, J. T. (2010). Loneliness matters: A theoretical and empirical review of consequences and mechanisms. Annals of Behavioral Medicine, 40(2), 218-227. https://doi.org/10.1007/s12160-010-9210-8
10. ↗ Holt-Lunstad, J., Smith, T. B., & Layton, J. B. (2010). Social relationships and mortality risk: A meta-analytic review. PLoS Medicine, 7(7), e1000316. https://doi.org/10.1371/journal.pmed.1000316
11. ↗ Holt-Lunstad, J., Smith, T. B., Baker, M., Harris, T., & Stephenson, D. (2015). Loneliness and social isolation as risk factors for mortality: A meta-analytic review. Perspectives on Psychological Science, 10(2), 227-237. https://doi.org/10.1177/1745691614568352
12. ↗ Kahlon, M. K., Aksan, N., Aubrey, R., Clark, N., Cowley-Morillo, M., Jacobs, E. A., Mundhenk, R., Sebastian, K. R., & Tomlinson, S. (2021). Effect of layperson-delivered, empathy-focused program of telephone calls on loneliness, depression, and anxiety among adults during the COVID-19 pandemic: A randomized clinical trial. JAMA Psychiatry, 78(6), 616-622. https://doi.org/10.1001/jamapsychiatry.2021.0113
13. ↗ Li, S., Stampfer, M. J., Williams, D. R., & VanderWeele, T. J. (2016). Association of religious service attendance with mortality among women. JAMA Internal Medicine, 176(6), 777–785. https://doi.org/10.1001/jamainternmed.2016.1615
14. ↗ Masi, C. M., Chen, H.-Y., Hawkley, L. C., & Cacioppo, J. T. (2011). A meta-analysis of interventions to reduce loneliness. Personality and Social Psychology Review, 15(3), 219-266. https://doi.org/10.1177/1088868310377394
15. ↗ Office of the U.S. Surgeon General. (2023). Our epidemic of loneliness and isolation: The U.S. Surgeon General’s advisory on the healing effects of social connection and community. U.S. Department of Health and Human Services. https://www.hhs.gov/sites/default/files/surgeon-general-social-connection-advisory.pdf
16. ↗ Smith, K. J., Gavey, S., Riddell, N. E., Kontari, P., & Victor, C. (2020). The association between loneliness, social isolation and inflammation: A systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews, 112, 519-541. https://doi.org/10.1016/j.neubiorev.2020.02.002
17. ↗ Valtorta, N. K., Kanaan, M., Gilbody, S., Ronzi, S., & Hanratty, B. (2016). Loneliness and social isolation as risk factors for coronary heart disease and stroke: Systematic review and meta-analysis of longitudinal observational studies. Heart, 102(13), 1009-1016. https://doi.org/10.1136/heartjnl-2015-308790
18. ↗ VanderWeele, T. J., Li, S., Tsai, A. C., & Kawachi, I. (2016). Association between religious service attendance and lower suicide rates among US women. JAMA Psychiatry, 73(8), 845-851. https://doi.org/10.1001/jamapsychiatry.2016.1243
19. ↗ Wang, F., Gao, Y., Han, Z., Yu, Y., Long, Z., Jiang, X., Wu, Y., Pei, B., Cao, Y., Ye, J., Wang, M., & Zhao, Y. (2023). A systematic review and meta-analysis of 90 cohort studies of social isolation, loneliness and mortality. Nature Human Behaviour, 7(8), 1307-1319. https://doi.org/10.1038/s41562-023-01617-6
20. ↗ Woo, C.-W., Koban, L., Kross, E., Lindquist, M. A., Banich, M. T., Ruzic, L., Andrews-Hanna, J. R., & Wager, T. D. (2014). Separate neural representations for physical pain and social rejection. Nature Communications, 5, 5380. https://doi.org/10.1038/ncomms6380