The National Football League Players Association selected Harvard for the study, the Boston Globe reported Monday.
About 1,000 retired NFL players will take part in the 10-year study.
Specialists from the university's many schools and affiliated hospitals will examine a range of factors among the players: repetitive brain traumas, torn knee ligaments, arthritic joints and even the effects of long-term exposure to acute pain and chronic use of painkillers.
The goal of the study is to improve the health of players within five years. White men in the United States have an average life span of 78 years, and African-American men, about 70, the researchers wrote in a summary of their project.
However, American and Canadian professional football players usually live on average to their mid-to-late 50s.
More than 100 lawsuits have been filed against the NFL claiming health problems from concussions.
Frustrated by the lack of attention to the issue, the players union allocated $11 million a year for research from its 2011 bargaining agreement.