Loneliness is an affective state stemming from perceiving less social connectedness than desired. Loneliness accelerates ageing and the onset of age-related diseases such as cardiovascular disease and Alzheimer’s disease. 

Although research has linked loneliness to the activation of various brain regions, social affective neuroscience is moving toward a network neuroscience approach which recognizes that affective states emerge from complex processes performed by networks of brain regions. Given the allostatic-interoceptive system’s (AIS) structure and function, it was studied as a target for understanding how loneliness may impact the brain through the years. 

The structure and function of the allostatic-interoceptive system

The AIS is a brain system that supports bi-directional communication between the brain and the peripheral body, which allows the brain to predictively regulate the body (meaning to engage in allostasis) by running model of the body’s needs relative to predicted demands from the outside world. Kleckner and Zhang have used seed-based functional connectivity (FC) analyses on human resting state data to reveal the existence of a singular functional system comprised of the brain’s broadscale networks.

Objectives of the research: understand the interaction between age, loneliness and the brain

This study examines the association between the patient’s age and the static (sFC) and dynamic functional connectivity (dFC) characteristics of the AIS in pleasant and unpleasant contexts, and how the associations differed at different levels of loneliness.

A new task was designed in which participants were engage in neutral, pleasant and unpleasant imagery about personally relevant social others. It is particularly relevant to examine the effect of loneliness on AIS functioning during induced affective states, as AIS responding during rest may differ from its responses to socio-affective stimuli. Functional connectivity, especially dFC, may have additional implications in behavioural tasks than in the resting state. Computed sFC and dFC metrics of the AIS have help hypothesised that loneliness and age would interact to predict different patterns of AIS functional connectivity during task-induced social neutrality versus social pleasure and displeasure.

Methodology: an approach combining neurosciences and personal experience 

Participants and procedure

Eighty participants were recruited for a larger study investigating associations between brain FC and well-being. The study involved neuropsychological testing, seven days of daily loving-kindness meditation practice, and brief self-report measures on their emotions and social experiences, an extended self-report questionnaire on the seventh day where they reported loneliness during the past week, and an fMRI scan session on the eighth day. Only participants’ age, data from the neuropsychological testing (for cognitive inclusion criteria), the self-report questionnaire on the seventh day, and the fMRI scan session are used in the current analyses.

Analyses

In order to test the effects of task condition, age and loneliness on AIS connectivity, four separate multilevel models were run for each AIS connectivity metric:

• Participation coefficient computed on static functional connectivity (static PC)
• Weighted degree computed on static connectivity (static WD)
• Participation coefficient computed over time-varying connectivity (dynamic PC)
• Weighted degree computed on dynamic connectivity (dynamic WD)

For each model using a given connectivity metric as the criterion, task condition was entered as the sole fixed predictor in the first step to examine any effect of the task design itself. Age, loneliness, and counterbalanced condition were entered at the second step, and the three-way interaction among task condition, age, and loneliness was entered at the third step. Finally, to test the specificity of loneliness effects, we replaced loneliness with the closeness ratings participants provided for their visualized individuals for each of the above 3-way interaction models.

Discussion

The current study examined how loneliness and age may interact to predict static and dynamic brain FC of the AIS, a brain system hypothesized to predictively regulate the state of the body in response to external demands, especially those that are socially salient. We found that age-related differences in AIS FC were more pronounced for those with higher loneliness.

The findings that loneliness exacerbated age-related effects on AIS static and dynamic FC are consistent with other evidence that loneliness may exacerbate normative ageing (Simons et al. 2023). First, we found that loneliness and age interacted to predict decreased static WD, or internal coherence, of the AIS. Those participants who reported higher loneliness showed a stronger negative association between age and AIS static WD when imagining social affiliation with an acquaintance.

These findings were not accounted for by individuals’ ratings of felt closeness during the social pleasure induction. Therefore, as adults age, those with higher loneliness may see more decrease in the functional efficiency of the AIS, especially during socially pleasant states. Notably, the least lonely individuals showed no age-related difference in AIS static WD during social pleasure, suggesting that low loneliness may be associated with sustained ability to benefit from social pleasure as adults age.

Moreover, lower dynamic FC may therefore reflect lonelier individuals’ decreased ability efficiently respond to socially pleasant and unpleasant situations at older age.

Limitations and future directions

Several limitations should be noted when interpreting findings from this study. First, this study sampled healthy individuals whose self-reported loneliness was low on average and who were younger than 70. Participants with many physical and mental health conditions were explicitly excluded from this sample, which may have limited both severely lonely and older adults from enrolling.

It is necessary to note that in this relatively healthy sample, even low levels of loneliness appear to impact AIS functional connectivity in older age. Future research is warranted to extend these results to individuals who are suffering from higher levels of loneliness.

Loneliness: an underestimated driver of brain ageing 

The current study is the first to examine age-related differences in both static and dynamic FC of the AIS during induced social affect and as altered by loneliness. These findings bring insights into how the brain regulates the body as adults age, as associated with socio-affective experiences such as loneliness. Moreover, the use of task-induced social affect and the examination of both static and dynamic FC bring methodological advancement for future research to further uncover mechanisms of affective and neurophysiological ageing.

Sources

Cacioppo JT, Patrick W. (2008). Loneliness: Human Nature and the Need for Social Connection. W W Norton & Co, xiv, 317.

Hawkley LC, Cacioppo JT.  Aging and loneliness: downhill quickly?  Curr Dir Psychol Sci  2007;16:187–91. 10.1111/j.1467-8721.2007.00501.x

Hawkley LC, Cacioppo JT.  Loneliness matters: a theoretical and empirical review of consequences and mechanisms. Ann Behav Med  2010;40:218–27.

Kleckner IR, Zhang J, Touroutoglou A, et al.  Evidence for a large-scale brain system supporting allostasis and interoception in humans. Nat Hum Behav  2017;1:0069. 10.1038/s41562-017-0069

Zhang J, Chen D, Deming P  et al.  Cortical and subcortical mapping of the allostatic-interoceptive system in the human brain using 7 Tesla fMRI. Nat Neurosci  2025;28:2380–91.Pessoa L.  On the relationship between emotion and cognition. Nat Rev Neurosci  2008;9:148–58. 10.1038/nrn2317