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• A recent study found that, over time, stressful relationships may accelerate biological aging.
• The researchers refer to those who create problems or make life more difficult as “hasslers.”
• The study also found that a greater number of “hasslers” in your life can lead to a higher risk of depression, anxiety, and poorer overall health.

Spending time with someone who consistently creates problems or makes life more difficult can accelerate biological aging and affect your overall health.

A recent study found that spending more time with people the researchers call “hasslers” and having more of them in your life can negatively affect various aspects of your life and health.

The researchers also noted that “social relationships are fundamental to human health.”

However, past research has mostly focused on the supportive nature of these relationships. This recent study focused on the “hasslers” in the close social networks of individuals and the role these stressful people play.

“Those around us can either increase or decrease our stress levels because we are wired for social connection and our social relationships can significantly influence and shape our mood, perspectives, motivation, and energy, on a daily basis, and for future goals/visions,” said Menije Boduryan-Turner, PsyD, licensed psychologist, and founder of Embracing You Therapy. Boduryan-Turner was not involved in the study.

The study analyzed data from 2,345 participants in a health survey in Indiana. The participants ranged in age from 18 to 103, with an average age of about 46.

The individuals answered questions about their relationships, focusing on the previous 6 months.

The researchers defined “hasslers” as people whom the participants reported as “often hassling them, causing them problems, or making life difficult.”

The average network size among participants was just over 5, with a maximum size of 25. On average, the individuals reported around 8.1% of the network members as “hasslers.”

Of the participants, 28.8% reported having at least one “hassler” in their social network, and 10% reported having two or more. This suggests that persistently negative ties are not rare among personal relationships.

“We resonate with people, and when someone creates problems, ideally, we would leave such a situation,” said Alex Dimitriu, MD, double board certified in psychiatry and sleep medicine and founder of Menlo Park Psychiatry & Sleep Medicine, who was not involved in the study.

“Dealing with a hassler definitely takes a toll on mental health, and I see that in my work every day,” Dimitriu told Healthline.

The researchers then examined the association between having “hasslers” in your life and biological aging.

They compared biological aging using saliva samples from participants, enabling the researchers to measure specific epigenetic markers.

This analysis showed a clear pattern. For each “hassler” a person interacted with, their biological aging pace increased by about 1.5%. This means that someone with an extra difficult person in their life may age about 1.015 biological years for each chronological year.

It’s important to note that this study does not definitively show that having difficult people in your life directly causes aging.

The researchers observed an association between “hasslers” and the rate of aging. They also noted that certain groups of people may be more likely to have or report “hasslers” in their lives.

Females were less likely than males to report having zero “hasslers” in their social networks. They also reported higher levels of “hasslers” in their lives in general than males.

There were also various psychosocial factors that emerged as important predictors of the presence of “hasslers.”

For example, individuals with adverse childhood experiences were more likely to have “hasslers” in their social network.

People with a larger social network were less likely to report zero “hasslers” and were more likely to have a higher number.

Daily smokers and people with less favorable health were also less likely to report zero “hasslers.” This suggests that “hassler” exposure is not random. Rather, it clusters around certain individuals with greater psychosocial and health vulnerabilities.

“Hasslers” were also more likely to be family members, with parents and children more likely to be reported as difficult than spouses.

Outside of the family, participants were more likely to report co-workers, neighbors, and roommates as “hasslers” than friends.

The researchers also examined whether the association with “hasslers” was specific to biological aging or extended across health outcomes.

They found that the number of hasslers in a person’s social group was consistently associated with worse health across multiple domains. The strongest associations were among mental health outcomes.

Each additional “hassler” was associated with an increase in the severity of both depression and anxiety. This was followed closely by less favorable self-rated mental health outcomes.

“When stress becomes too hard to manage, it creates insomnia, poor concentration, depression, anxiety, and/or irritability,[an] increase and/or a decrease in appetite, isolation, and paralysis,” said Boduryan-Turner.

The associations found with physical health and adiposity-related (excess fat) outcomes were more modest, but still significant.

Additional “hasslers” were associated with:

“Stress can increase our blood pressure and affect our gastrointestinal and immune systems, among many other organ systems in the body,” Nissa Keyashian, MD, board certified psychiatrist and author of “Practicing Stillness,” who was not involved in the study, told Healthline.

Many may say that the obvious solution is to reduce contact with “hasslers” in your life. However, this may not always be possible. Certain people, such as family members or co-workers, may be part of your daily life.

Dimitriu recommended that you control what you can, which is most often yourself. A strong emphasis on self-care, time to journal, and grounding yourself through meditation, exercise, or both is essential.

Boduryan-Turner said that it is fundamental to set clear, value-based boundaries.

“The keyword here is value-based, because often we make fear-based decisions. When setting boundaries, we want to keep our values in mind and communicate our needs from that place,” she added.

Keyashian agreed. “Practicing setting healthy boundaries is one of the most important skills in our lives,” she said.

Boduryan-Turner noted that people should set limits with love.

“We can set our boundaries lovingly and compassionately,” she said. “It doesn’t have to feel like a fight or a conflict to set them. Often taking breaks and engaging in activities that soothe are necessary ways to cope with these kinds of people in our lives.”

• Federal regulators have approved leucovorin for the treatment of cerebral folate deficiency, a rare neurological disorder.
• The FDA approval, however, did not include the use of leucovorin as a treatment for autism.
• The Trump administration has touted leucovorin as an autism treatment, but experts agree that more research is needed before leucovorin should be approved for this purpose.

A medication used primarily to help relieve the side effects of chemotherapy has been given the green light to be used as a treatment for a rare neurological disorder.

Officials at the Food and Drug Administration (FDA) announced on March 10 the approval of the drug leucovorin to help treat adults and children with cerebral folate deficiency. This rare condition is characterized by low levels of vitamin B9 in the brain.

However, the FDA announcement did not mention the use of leucovorin as a potential treatment for autism.

In September 2025, President Donald Trump and other administration officials suggested that the FDA had started a process to approve leucovorin as a treatment to manage symptoms in autistic people. However, there’s no word yet on a timetable or process for such an approval.

Leucovorin is the first approved treatment for cerebral folate deficiency. The FDA decision is being praised as long overdue relief for individuals with that condition.

“Today’s approval represents a significant milestone for patients living with cerebral folate transport deficiency due to the FOLR1 variant, a rare genetic condition that has had no FDA-approved treatment options until today,” said FDA commissioner Marty Makary, MD, in the agency’s announcement.

Leucovorin is a prescription medication used mainly to reduce the toxic side effects of chemotherapy agents such as methotrexate.

The medication works by helping to restore folic acid to healthy cells that have had that substance depleted by the effects of chemotherapy.

Leucovorin is considered to be effective as a “rescue agent” for people undergoing certain types of chemotherapy.

• developmental delays
• seizures
• movement abnormalities

It’s estimated that 1 in 1 million people worldwide have cerebral folate deficiency, although the true prevalence is unknown. It’s also been estimated that 38–70% of autistic children may have cerebral folate deficiency.

However, experts say those percentages may be inflated because much of the data has been drawn from FRAT tests, a blood exam that can be inaccurate.

While individuals with cerebral folate deficiency may have a higher risk of autism, but autistic people don’t necessarily have a higher risk of cerebral folate deficiency.

Alycia Halladay, MD, the chief science officer for the Autism Science Foundation, said she’s glad that people with cerebral folate deficiency finally have a treatment.

“This will probably help them. The mechanism is there,” she told Healthline. “I feel any relief would be helpful.”

Antonio Hardan, MD, a professor of psychiatry and behavioral sciences at Stanford University, said that early intervention with leucovorin for cerebral folate deficiency is key.

“Case reports [support] complete clinical and radiological recovery when treatment is provided before the age of 2 years,” Hardan told Healthline.

While early intervention in autism is also crucial, it’s too soon to recommend leucovorin as a treatment.

Halladay expressed relief that leucovorin wasn’t approved as an autism treatment because there isn’t yet a scientific justification for this particular use.

“I’m glad the FDA used a scientific approach and used rigor to make this decision,” she said.

Hardan echoed this sentiment. “There is some evidence from small randomized controlled trials supporting the use of leucovorin for the treatment of autism. However, these studies have several design limitations, including small sample sizes and non-rigorous inclusion/exclusion criteria,” he said.

In September, President Trump said the approval of leucovorin as an autism treatment would give “hope to the many parents with autistic children that it may be possible to improve their lives.”

Makary echoed that sentiment, estimating that “hundreds of thousands of kids, in my opinion, will benefit” from the approval of leucovorin.

After that press briefing, officials at the Health and Human Services (HHS) Department clarified those comments, saying that leucovorin “is not a cure” for autism and “may only lead to improvements in speech-related deficits for a subset of children.”

The research on leucovorin and autism has mostly consisted of small studies with fewer than 100 participants, many done repeatedly by the same researchers.

The results of one of the studies, published in the European Journal of Pediatrics, were retracted in January after the authors identified several errors in their data.

There has been some anecdotal evidence that leucovorin can provide some benefits to communication and behavior for some autistic children, specifically those with cerebral folate deficiency or evidence of folate metabolic differences.

According to the American Academy of Pediatrics (AAP), however, more research in this area is still needed.

“The evidence for leucovorin and use for autism is currently limited,” the AAP said in an FAQ sheet about leucovorin use in autism and cerebral folate deficiency.

“Small studies show benefits to communication and behavior for some autistic children, specifically those with CFD or evidence of folate metabolic differences. Larger independent trials are warranted to better understand which patients may benefit. More evidence on efficacy and safety is needed before pediatricians can broadly recommend leucovorin,” the AAP said.

The Autism Science Foundation agreed, saying more studies are needed before leucovorin can be considered as a treatment for autism.

Halladay said that large-scale studies that examine safety and efficacy need to be completed before leucovorin can be considered as an autism treatment.

An HHS official appeared to agree, telling NBC News this week that there is not enough data to support leucovorin’s use as an autism treatment.

“We don’t have sufficient data to say that we could establish efficacy for autism more broadly,” the official said. “It’ll be up to patients to talk with their physicians to see if that might be right for them.”

Doctors can prescribe leucovorin as an off-label treatment for autistic children. Some have apparently been doing so.

A recent report published in The Lancet stated that leucovorin prescriptions for children rose 71% during the 2 months following President Trump’s announcement in September.

Halladay expressed concern about that increase, as well as the fact that people can go online and purchase folate acid products with vitamin B9 that are similar to leucovorin.

“All this can lead to false hope from companies that prey on families who will do anything to help their child,” she said.

Halladay encouraged families of autistic children to listen to medical professionals over what they read in the media.

“Talk to your doctor. Listen to your doctor and don’t listen to the internet,” she said.