There is something refreshing about scientists confessing their ignorance. Day after day, in research journals and at international meetings, they strut, cluck and boast about the latest enigma they've wrestled to the ground. The entire human genome mapped! The farthest star plotted! The mating habits of dinosaurs inferred from fossilized eggs! Ordinary folks can be excused for muttering, "Is there nothing these white-coated brainiacs don't think they know?"

This week the world's largest general science journal, aptly named Science, takes a different and more humble tack, presenting a list of the 125 biggest quandaries that scientists have failed to fathom.

This catalogue of bewilderment, part of the journal's 125th anniversary celebration, is the product of a months-long survey of more than 100 leading researchers in myriad disciplines, who were asked to focus on questions that have a chance of being answered in the next 25 years. Beyond offering a glimpse of the many nagging gaps remaining in the human knowledge base, it reveals the enormousness of scientists' ambitions and the great versatility of the scientific method, which has proved so valuable as a way to make sense of the unknown.

"Reading through the questions gives a wonderful sense of all the incredibly intriguing things scientists are looking at these days," said Colin Norman, Science's news editor, who ushered the initial list of submissions through 17 versions to get it down to a mere 125.

Here is a sampling of the mysteries that scientists themselves most want to solve:

What is the universe made of?

The answer may seem obvious: matter and energy. But physicists who have been studying the details have some disturbing news. If you take every atom in the universe, and all the detectable energy in and around them, it adds up to less than 5 percent of what has to be out there, as determined by how the galaxies are behaving. Scientists have concluded that in addition to ordinary matter, there must also be "dark matter" -- mysterious stuff that gets the universe up to about 30 percent full. That leaves 70 percent of the universe consisting of "dark energy," a nice name for something that no one has a clue about.

A related question: Is ours the only universe? Many cosmologists suspect the answer is "no." Ours may be just one of countless universes in a "multiverse" that is bubbling with big bangs. To settle that question, a related query will have to be answered in the affirmative: Is it even possible to know anything beyond our universe?

How much can the human life span be extended?

Human life spans have stretched amazingly in the past few hundred years. In the 20th century alone, the average U.S. life span grew to 77 years from 49, an increase of more than 50 percent.

The longest any person is known to have lived is 122 years. That was Jeanne Calment, a Frenchwoman who died in 1997. No one knows why she lived that long (she smoked cigarettes until she was 97, when she quit for her health). Perhaps it was her wry sense of humor. Asked on her 100th birthday what kind of future she anticipated, she responded: "A very short one."

In general, scientists reckon that longevity is the result of a unique combination of genetics and life habits, and they suspect that with attention to those things the average human life span can be increased substantially.

Experiments on simpler organisms, such as the millimeter-long soil-dwelling nematode worm Caenorhabditis elegans, indicate that in some species a change in a single gene can double life span -- though in that case we're talking about a total of six weeks. Other experiments with humans' closer relatives, mice and monkeys, strongly suggest that by cutting out the greater part of our dietary intake we might increase our life span by decades -- though we'd spend a lot of those longer lives fantasizing about our next meal.

Should scientists succeed in making centenarians a sizable voting bloc, watch for new questions about Social Security.

What genetic changes made us uniquely human?

There are those who argue that shoes make the man. But scientists can't help but note that even a chimpanzee in Cole Haans lacks the humanity of a barefoot beggar. What exactly is at the heart of that species difference has been a matter of shifting attentions, as the old delineators -- language, tool use, culture, an ability to laugh -- have each in their turn been found in one animal or another. Now, in what some might see as a desperate effort to retain our sense of specialness, the hunt for the essence of humanness has turned to the genome.

Comparisons of the human genetic code's 3.1 billion DNA letters and those of our nearest relatives, chimpanzees, confirm long-held suspicions that by this measure we differ by only about 1 percent.

A few genes seem to have been crucial to human evolution, such as one that allowed our skulls to accommodate bigger brains and one that seems to have facilitated the development of language. But clearly there is a lot more going on than that. And no one has come close to finding the gene that, against all evolutionary logic, drives some male hominids to wear shoes with leather tassels.

Are we alone in the universe?

Six billion of us and counting -- not to mention the countless other species with whom we share this precious planet -- and still we struggle with loneliness. Giant radiotelescopes point plaintively to the heavens, listening for reassuring evidence of extraterrestrial companionship from someone, anyone, green or otherwise.

Scientists have scanned more than 700 star systems for the subtlest peeps of life, using the mother of all remote controls to listen simultaneously on millions of channels. Assuming the universe is as it appears -- filled with galaxies that are filled with suns that are surrounded by planets, no small number of them doubtless like our own -- the odds are overwhelming that there is a lot of other life out there, and that some may be pointing telescopes at us.

With bigger and better scanning arrays being built every year, many scientists not usually prone to exaggeration think we could be within a generation of making contact with some version of our biological brethren. Assuming, of course, that the reruns of "Gilligan's Island" that have been arcing across the cosmos have not convinced our distant neighbors that their children should find other friends.

Who wants to know?

Or, as Science magazine puts it, "What is the biological basis of consciousness?"

This question is an oldie, dating at least to the beginnings of humankind. It underwent its last big renovation in the 17th century, when the French philosopher Rene Descartes declared that the mind and the body lived in different dimensional spaces and so, like east and west, would never meet.

That model has lately begun to metamorphose amid evidence that body and mind have a far more integrated and interesting relationship. But the scientific method, which insists on complete objectivity, faces some of its biggest challenges as researchers contemplate experiments that would turn the mind's attention to the task of understanding itself.

The list of questions goes on. How do organs and organisms know when to stop growing? Why do we sleep? What are the limits of learning by machines? Is morality hard-wired into the brain?

It's endless, with every answer cultivating a new crop of questions. But that's the point.

"This is what scientists do," Norman said, "they ask questions."

The full list of 125 questions, with essays devoted to the top 25, is at www.sciencemag.org/sciext/125th.