You are not running out of time

Beg to differ. I'd say that if you're not feeling pressed, that you have too little time left, then you don't have anywhere near an adequate view of the plausible future. A golden age lies ahead, of glittering marvels to make all that has come so far pale to insignificance. But unless we step up to the plate and master biotechnology a lot faster and better than is presently managed, all of us reading this now will miss both that future and lives of health and transcendence lasting centuries in which to enjoy it.

As I put it here:

http://hplusmagazine.com/2011/07/13/longevity-science-needs-...

"We all express the symptoms of a fatal, inherited degenerative condition called aging - or so the joke goes. It's a dark joke, but there's truth to be found in it, as is often the case in black humor. Unfortunately, all too few people think of themselves as patients suffering aging, and fewer still would call themselves patient advocates, agitating for research leading towards therapies and cures for aging. This is a sorry state of affairs: given that our time is limited and ticking away, the tasks upon the table should always include some consideration of aging. What can we do about it? How can we engineer a research community, funding and support to make real progress within our lifetimes? If you don't spend at least some of your time on this issue, then you're fiddling while Rome burns. Time is the most precious thing we have, and we live on the cusp of technologies that will allow us to gain more of it - but those advances in medicine won't happen soon enough unless we work at it."

I generally agree with the sentiment, but it seems like the author never really shed the dependence on having an arbitrary material goal.

I think a more Zen-like direction is to just apply the "friend in a pub" test - if you can describe your motivations and actions to an (intelligent) peer and have them nod in approval, then that's it. And yes, there are many such choices, which is the whole point - it doesn't really matter beyond that threshold!

I remember that moment of epiphany for myself, when I realized that nobody else really gives a shit what specifically I do, as long as it's a reasonably fine decision.

And no, that does not mean slacking/etc. Wasting one's potential is definitely not reasonable.

That's very difficult to predict, though! There is some correlation with short-term success, but not that great correlation; there are plenty of people "famous in their day" forgotten 20 years past their death, and a substantial number of people whose work only seemed important in retrospect, or after it was recontextualized by a later writer who somehow dug up some obscure work and took a liking to it. I have a minor personal hobby of translating encyclopedia entries from the Allgemeine Deutsche Biographie, the main German-language biographical encyclopedia of the years 1875-1912, into the English Wikipedia, and it's amazing how the space that the writer of the time saw fit to devote to a person often correlates badly with a 21st-century assessment of the person's importance.

Of course, that doesn't quite tell you what to do about it. I personally tend to lean towards, do something that seems interesting to me, with the caveat that I also need to eat. I'm not as worried about making a name for myself 500 years from now, although "seems interesting to me" probably includes some part of that evaluation in it (things that seem likely to outlast me probably get a boost in my personal evaluation of interestingness).

A key mental transition to make is from asking the question "am I winning?" to asking the question "am I doing something worthwhile?"