Sometimes, all we can do is try to give information when the opportunity presents itself, and at home or discreetly. My son is a year older, and he's asked about 'why people are fat'; we talk about why in a nonjudgmental way and then I tell him "People who are fat don't like to be told they are fat. It might hurt their feelings and they already know. You can ask them about something else." (I have a friend who is a big woman; this is what she told another friend's daughter when asked "Are you fat?")
We also use picture books and sometimes talk about how faces have wrinkles, how people all have different kinds of bodies, different colors of skin (there's a book by Katie Kissinger, "All the Colors We Are" which I use with my preschoolers), different ways of dressing. Some people use a wheelchair or some use a scooter to get around. Some people have legs and arms from their body, and some have other things to help. We have a few people in our midst who are friendly and have either a prosthetic leg or hooks/fewer fingers, etc. Giving a positive reflection of why people are different in appearance sometimes minimizes the 'fear' aspect some kids might have and instead may open up a conversation with curious kids. I don't usually mention differences until I see a child is noticing them or hear it being discussed, otherwise it can be confusing to do too much explaining.
As for how to handle it in the moment: you can try positive affirmation sometimes. "She looks old!" can be met with "You know, she is older than you or I am. I'll bet she has some good stories from when she was a little girl."--this opens a door of sorts, conveys respect and dignity. The same with "That person is (color of skin)" --a common one. "Yes, they get that skin color from their parents. Just like you do." A fact, and it actually points out a commonality (we *all* inherit our skin color from our parents and ancestors) instead of focusing on difference.
Sometimes, too, there's no saving the situation. Last year on the bus, a man with many teeth missing was engaging my then newly-four year old son. After a few back-and-forths between them, my son looked concerned and asked "What happened about your mouth?" Mortified. There wasn't time to even say a word before the man muttered "Well, some of my teeth came out and I'm going to get my false teeth next week." A few stops later, he moved away from us. A bit later, off the bus but while the memory was still fresh, I mentioned to him that when people are missing teeth, they already know... and they might feel bad about it, so we don't need to talk about it. We can talk about something else. I think teaching the compassionate angle helps, too.