Research has long shown the health risks of loneliness and the healing power of social connection. But a growing literature indicates that relationship quality — not just the number of social ties — also matters for physical and mental health.

Evidence suggests that negative social ties can accelerate aging, increase inflammation, and trigger downstream biological processes that worsen health outcomes even when people are not socially isolated.

“We always have a feeling that dealing with these people in our lives causes some kind of mental and emotional drain,” said Byungkyu Lee, PhD, an assistant professor of sociology at New York University, New York City. “But it is not just a feeling — it has a biological imprint.” Advances in tracking and analyzing epigenetic biomarkers now allow scientists to see that imprint directly.

These data offer clinicians new insight when evaluating chronic conditions or patients who do not respond to treatment. As a biopsychosocial model gains traction for managing chronic and complex conditions, experts are urging clinicians to consider their patients’ social health, particularly the presence of strained relationships.

The Cellular Toll of Relational Stress

In a recent study of 2345 adults coauthored by Lee, nearly 30% reported at least one close contact who “often” caused problems or made life difficult. About 10% reported two or more. Saliva samples revealed differences in DNA methylation — chemical markers on DNA that reflect aging at the cellular level.

The researchers used two complementary methylation clocks: DunedinPACE functions like a speedometer, estimating how fast a person is aging in real time, Lee said. GrimAge2 works like an odometer — measuring accumulated biological aging relative to chronological age.

People reporting one negative social tie showed a 2.6% faster pace of aging and 15 months of accelerated biological aging. Each additional negative tie was associated with about another 1.5% increase in speed of aging and 9 more months of biological age — that’s 13%-17% the increased rate of aging seen in smokers, the researchers noted in the study.

Negative social ties were also associated with worse mental and physical health, higher rates of depression and anxiety, elevated markers of inflammation, a higher BMI, and a greater number of diagnosed chronic conditions. The negative health links were strongest when the difficult person was a family member rather than a spouse, perhaps because family tends to be the most “embedded” in people’s lives in a way that’s not easy to “detach from,” Lee said.

From Conflict to Inflammation

“Negative interactions essentially act as chronic stressors,” said Viola Vaccarino, MD, PhD, a professor of epidemiology and medicine at Emory University, Atlanta. “We know that stress can affect chronic conditions in terms of risk and severity, as well as general health and well-being.”

Relational stress can fuel inflammation, disrupt autonomic function, and impair vascular health so vessels struggle to relax and deliver blood to the heart, Vaccarino said. It also activates the sympathetic nervous system, triggering a range of physiologic responses — such as vasoconstriction, increased blood pressure, and faster heart rate — that can wreak havoc throughout the body over time.

Clinical health psychologist Janice Kiecolt-Glaser, PhD, director of the Ohio State Institute for Behavioral Medicine Research, has documented acute spikes in stress hormones like norepinephrine (which promotes inflammation) when couples discuss marital problems with their partners. “When people were more negative or nasty to each other, stress hormones increased,” she said. Over time, this repeated response could translate to chronic inflammation. “We assume that what we see in the laboratory is just a snapshot of what happens in real life.”

Stress and depression have repeatedly been shown to reduce medication adherence, and that link also applies to relational stress, Vaccarino said. In a 2021 study of more than 1800 adults with uncontrolled hypertension, greater perceived stress was independently associated with lower odds of taking medication as prescribed. By contrast, social support has consistently been associated with greater medication adherence.

Relational stress can also blunt treatment response, Vaccarino said. Evidence suggests the health risks posed by negative close relationships may rival established risk factors like smoking, high BMI, and physical inactivity. A patient whose blood pressure won’t come down could very well be up against chronic relational stress, Vaccarino said.

Bringing Social Health to Clinical Care

Lee urged physicians to recognize that negative social ties can be overlooked in health assessments. “We tend to focus on social isolation,” he said. Making patients aware of the health risk associated with negative relationships may help mitigate its effect.

Vaccarino agreed. “Try to uncover any stress that patients might be enduring,” she said. Lee recommends physicians specifically ask about “hazardous” people who may be making a patient’s life difficult.

Despite the well-recognized connection between psychosocial stress and physical health, the focus in busy clinical settings remains on traditional risk factors, Vaccarino said. “There is usually no discussion of other aspects.”

Short patient surveys can help surface relational stress ahead of appointments. Some practices routinely screen for depression. This is standard for cardiovascular patients at Kiecolt-Glaser’s institution and can serve as a window to relational stress, she said.

Translating this research to the clinic has limits. “We do not have strong tools on how to intervene to ameliorate these risks,” Vaccarino acknowledged, “and these things are really hard to change in people’s lives.”

For now, experts pointed to stress-reduction strategies such as regular exercise, meditation, and boundary setting. Also, expanding positive social support networks “might be a way to actually avoid or reduce the problem of having negative ties,” Lee said.

The experts cited in this article had no relevant disclosures.