I've hard this umpteen times this year; from folks ranging from 21 to 45; and it breaks my heart to hear the pain. I've heard it four times this week.
I never had this particular concern. Not in that way. I'm still feeling out the reason why; if it's a function of upbringing and culture; or my disconnection with my own passions vs my intellect/ego - or an ability to make myself happy (enough) with what I'm doing.
I wonder if this is a recent artifact; with the idea of following ones passion and being satisfied in ones own work being more prevalent than they were in my father's generation.
There's one other thought. There's a series of patterns and skills connected with work successes that have come over the years; regardless of whether the work is inspring - and I sometimes see how the absence of those skills/patterns works against those who are feeling lost, unsatisfied.
A series of disconnected observations without a conclusion. Life, I suppose.