The birth and subsequent expansion of this underground cemetery are related to the martyrdom of the young Agnes, buried here, and date back to the early third century AD. The saint was perhaps a victim of the persecution of Decius in 250 AD. or of Valerian in 257 AD, or of the later one from the time of Diocletian in 304 AD. Attested in the most ancient documents concerning the Roman martyrs, his cult was one of the most widespread in Rome in the early centuries of the Christian era.
The martyr's body was buried in a gallery on the first floor of a pre-existing Christian cemetery, divided into various regions and arranged on three levels, dug into the side of a hill along the Via Nomentana. In the area there were also numerous pagan burials, both of modest and monumental dimensions, dating back to the 1st and 2nd centuries AD. The pagan necropolis was destroyed when the emperor Constantine had a large basilica built in this area, of which few structures are visible today; the mausoleum of Santa Costanza was then annexed to this latter, which is considered one of the most important monuments of late ancient architecture.
On the place of Agnese's burial, a small church was built in the fifth century, completely rebuilt in the seventh century by Pope Honorius who transformed it into the current semi-underground basilica: its altar incorporates the martyr's tomb while a wonderful mosaic with Agnes between popes Honorius and Symmachus on a golden background decorates the apse. On the walls of the monumental staircase leading to the church there are two of the oldest testimonies of the cult of the saint, dating back to the fourth century: a marble slab with the depiction of the martyr and an inscription of Pope Damasus, discovered in 1728.
Although devoid of pictorial decorations, the catacombs have returned a large number of inscriptions, graffiti and objects of funerary use, for example a Constantinian monogram decorated with enamels or the epitaph of the alumna Sabina who wanted to be buried above the tomb of the adoptive parent.
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