in (a period of time, manner); at (a time, stage in life); while
Formal/literary expression used to indicate a time, stage, or manner in which something occurs. Often follows nouns or adverbial phrases.
He went abroad for the first time at the age of twenty.
Formal/literary concessive use, often with a sense of surprise or contrast. Follows nouns or nominalized phrases.
as well as; (both) ... and ...
Formal/literary listing pattern, often in the form AにしてB, meaning 'both A and B' or 'A as well as B'. Used with nouns or adjectival nouns.
Archaic locative use, equivalent to modern で or に. Found in classical texts; not used in modern Japanese.
He grasped the situation in an instant.
Even a master like him made this mistake.
This problem, although simple, is difficult.
He is both a scholar and a poet.
The dish is simple as well as delicious.
In classical language, it can indicate location, as in 'playing in the mountains'.
ながら is a common conjunction for 'while' or 'although', but にして is more formal and can also express 'at the time of' or 'both...and'.
Derived from the particle に combined with the conjunctive form of する (して). The exact historical development of its various senses is uncertain, but it likely evolved from a locative/temporal marker into concessive and listing uses.