Does it ever make sense to make a 2-story house into a 1-story home? We like our location but do not need the room anymore. We need a new roof, so this feels like the right time to make this big change if we're going to do it.
There's no structural reason you can't do this, barring an architect or engineer saying otherwise! It's more of an economic question. If you reduce the size of your home, you reduce its value accordingly. To get a sense of the economic impact, check out the values of single story vs two story homes in your area. Find homes sold recently that are the size of what your remodeled would be, and determine whether the reduced resale value, combined with the cost of the remodel, makes this project worth it.
Generally speaking, though, it's unusual to do things that reduce a home's value. You might be able to come up with some better, financially wiser solutions with the help of Certified Aging-In-Place Specialist (CAPS). Certified Aging-In-Place Specialists can connect you with designers, builders, and other pros who remodel homes to make them more accessible for aging residents.
If the challenge here is to simply make sections of your house more accessible as you age, there are far less drastic ways to do that. You can make these changes to your home in ways that actually add value, rather than detract from it. Consider all options before taking such a drastic step that could result in a major profit hit.