A large segment of white middle-aged Americans has suffered a startling rise in its death rate since 1999, according to a review of statistics published Monday that shows a sharp reversal in decades of progress toward longer lives.

The mortality rate for white men and women ages 45-54 with less than a college education increased markedly between 1999 and 2013, most likely because of problems with legal and illegal drugs, alcohol and suicide, the researchers concluded. Before then, death rates for that group dropped steadily, and at a faster pace.

An increase in the mortality rate for any large demographic group in an advanced nation has been virtually unheard of in recent decades, with the exception of Russian men after the collapse of the Soviet Union.

The rising death rate was accompanied by an increase in the rate of illness, the authors wrote in the Proceedings of the National Academy of Sciences.

[There’s a high suicide rate among elderly white men]

“Drugs and alcohol, and suicide . . . are clearly the proximate cause,” said Angus Deaton, the 2015 Nobel laureate in economics, who co-authored the paper with his wife, Anne Case. Both are economics professors at Princeton University.

“Half a million people are dead who should not be dead,” he added. “About 40 times the Ebola stats. You’re getting up there with HIV-AIDS.”

Death rate for U.S. non-Hispanic whites (USW), U.S. Hispanics and six comparison countries, aged 45-54. (Source: Proceedings of the National Academy of Sciences.)

Since at least 1970, Americans and residents of other wealthy countries have generally enjoyed longer and healthier lives, as smoking has declined, better treatments have been developed and preventive measures and lifestyle changes have had an impact.

[Overall death rates in the U.S. are dropping]

But Monday’s bleak findings could have far-reaching implications as the surviving members of this sizable segment of the population continue toward retirement and eligibility for Medicare, according to experts. A sicker population that has been less able to prepare for the costs associated with old age will place an increasing burden on society and federal programs, they said.

“This is the first indicator that the plane has crashed,” said Jonathan Skinner, a professor of economics at Dartmouth College, who reviewed the study and co-authored a commentary that appears with it. “I don’t know what’s going on, but the plane has definitely crashed.

“High school graduates [and] high school dropouts [are] 40 percent of the population,” he added. “It’s not just the 10 percent who didn’t finish high school. It’s a much bigger group.”

[2001 Paxil study seems to down play suicide risks in youths]

Death rates for other developed nations examined by the two researchers, as well as rates for U.S. blacks and Hispanics, continued their steady decline of recent decades. Whites in other age groups between 30 and 64, and more educated whites also had lower death rates. But the other age groups also experienced substantially higher death rates from drug and alcohol overdoses, suicide, chronic liver disease and cirrhosis of the liver.

Mortality by cause among white non-Hispanics ages 45-54. (Source: Proceedings of the National Academy of Sciences.)

While the death rate for African Americans is still greater than the rate for whites, the turnaround among whites is shocking because of the advantages they enjoy, said David Weir, director of the health and retirement study at the Institute for Social Research at the University of Michigan.

Typically, socioeconomic circumstances “gang up on African Americans, who have lower education, lower incomes and race all working against them,” said Weir, who also reviewed the study for the journal. “In this case, that’s not happening.”

[Understanding suicide, which is surprisingly common in spring]

Weir said economic insecurity, the decay of communities and the breakdown of families probably have had some impact on death and illness rates, in addition to the nation’s opioid epidemic and the factors the authors identified. But the study clearly shows they are not the result of diseases such as lung cancer or diabetes, which are declining and increasing slowly, respectively.

Death by poisoning, suicide, chronic liver disease and cirrhosis for white non-Hispanics of varying age groups. (Source: Proceedings of the National Academy of Sciences.)

“I think it has to have something to do [with] the pain underlying it,” both physical and psychic, he said. “That is the age when people have their midlife crisis . . . I think it has to do with that stage of life, and physical ailments do start to accumulate at that age.

“This paper really is a question, not an answer,” he added.

Case and Deaton were examining government statistics on death rates and illness when they discovered the spike in mortality for people ages 45 to 54 in the period between 1999 and 2013.

“We both were sort of blown off our chairs when looking at that,” Deaton said. He said they knew that most demographers would look at the numbers and say, “ ‘You’ve got to have made a mistake. That cannot possibly be true.’ ”

When they pored over the data, however, they found that mortality rates for this group had risen an average of a half percent per year since 1999, after falling an average of 2 percent annually for the 20 years before that. If mortality rates group had stayed on their steady downward course, a half-million more people would be alive today, they determined.

When they looked at illness (morbidity), “there was a large and statistically significant decline in the fraction reporting excellent or very good health” that was matched by increased reports of physical pain, according to the study.

[The man who knows more about death than anyone else]

The proportion of people who said they were in “serious psychological distress” also rose significantly, the research shows.

Deaton, awarded the Nobel prize for his work on individual consumption choices, has long studied measures of well-being, health and pain. He and Case authored a paper in June that found reports of physical pain “are strongly predictive of suicide in many contexts” and that reports of pain are increasing among middle-aged Americans.

Their findings have been corroborated by other research. A report from the National Heroin Task Force established by the Justice Department puts the number of overdose deaths from legal and illegal drugs at 110 every day. The heroin death toll has quadrupled in the decade that ended in 2013, according to the Centers for Disease Control and Prevention.

A study in the journal JAMA Psychiatry last year reported that 90 percent of the people who tried heroin for the first time in the last decade were white. Three-quarters said they were introduced to heroin through the use of prescription drugs.

In January, the CDC reported that an average of six people die every day because of alcohol poisoning and that 76 percent are ages 35 to 64. Three-quarters are men.

But just last week, researchers reported that the U.S. death rate for all causes declined 43 percent between 1969 and 2013, from about 1,279 per 100,000 people to about 730. The rate of death caused by strokes, heart disease and cancer all declined significantly, researchers reported in the Journal of the American Medical Association.