More than 20 million households contain Americans who look after loved ones, donating an estimated $250 billion a year in free care. While caregiving can offer enormous rewards–providing a sense of fulfillment, deepening lifelong loves–new research increasingly links it to deleterious health effects, including a weakened immune system, depression and even premature death. In one landmark study, Richard Schulz, of the University of Pittsburgh, found that elderly caregivers who said they felt physically or psychologically strained by their responsibilities were 63 percent more likely to die early than noncaregivers. With an aging population expected to double by 2030, researchers are alarmed about a caregiver crisis in the making. “It’s an issue of such great public-health significance,” says Schulz. “It boggles the mind as to how we’re going to handle it in the future.”

Caregiving takes a toll on the body in very tangible ways. Lifting a frail senior out of bed can injure the shoulders and back. The symptoms of arthritis or high blood pressure can worsen as caregivers neglect their own health. Kathie Crombie, 52, spent more than a year looking after her husband, Pete, who had stomach cancer. Before he died last month, she went to the ER with chest pains, a racing heart and nausea. Tests showed no serious maladies, leading her doctor to conclude it was caregiver stress. “Even when you think you’re able to handle everything,” she says, “you’re being torn up inside.”

Scientists are now zeroing in on what may be happening at the molecular level. At Ohio State University, Janice Kiecolt-Glaser and her husband, Ronald Glaser, have been studying the effect of caregiving on the immune system for more than a decade. Compared with a control group, caregivers of spouses with dementia have weaker responses to pneumonia and flu vaccines, and their wounds heal more slowly. Over a six-year time frame, the researchers also found that the stress hormone Interleukin-6, linked to heart disease, diabetes and arthritis, was four times higher in caregivers.

A mind full of worries can fuel depression: Will I have to move her to a nursing home? Is he in pain? How will I pay for medications? For years Dan Hanley, 71, bathed his wife, Doris, 71, who has multiple sclerosis. He prepared her feeding tube, he put on her favorite soap operas. The two are so close, says Dan, “it’s as though we’re one.” But as Doris’s condition worsened and friends withdrew, Dan started feeling helpless and isolated. Soon after surprising Doris with a 50th-anniversary party last year, he was plagued with suicidal thoughts: “My doctor said, ‘Either put Doris in a nursing home or you’ll wind up in the ground’.” Today Dan visits Doris twice a day at a nearby facility, but the depression persists. “I worry about her so much,” he says.

Left untreated, depression can lead to rare, but tragic, outcomes. Donna Cohen, of the University of South Florida, found that half the 176 homicide-suicides committed by older people over a six-year period in Florida involved caregivers. Most were men who seemed to be devoted husbands overwhelmed by their inability to look after their spouses, says Cohen: “It’s an act of depression and desperation.” Gladys Gonzalez-Ramos knows the agony. She saw her father become increasingly sad and frustrated by her mother’s Parkinson’s and his inability to save her. In the end, he took drastic measures with a handgun, killing his wife and then himself. They had been married for 52 years. “He felt he had lost his teammate,” says Gonzalez-Ramos.

There are ways to relieve the burden. Support groups offer lifelines out of isolation. Adult day-care programs provide respite. Regular exercise lowers blood pressure and reduces stress and depression. Most important of all: caregivers must look after themselves–without their own good health, their loved ones will suffer, too.