Feeling Old? Blame Your Nuclear Pores

22 January 2009 (All day)

Maximiliano D'Angelo

Changing of the guard. In these nuclei from muscle cells, yellow indicates where nuclear pore proteins are being replaced.

As if gimpy knees, clogged arteries, and forgetfulness weren't bad enough, new research has identified another way our bodies falter as we get older. The pores that permit only certain molecules to enter and exit the nuclei of our cells start leaking. A new study raises the possibility that permissive pores trigger some of the physical decline of old age.

Nuclear pores aren't mere portholes. Each consists of about 30 different proteins called nucleoporins that control what goes in and out of the nucleus. Scaffold nucleoporins form the channel through the nuclear membrane, and peripheral nucleoporins make up the pore's outer sections. Whenever a cell divides, it removes and rebuilds its nuclear pores. However, most cells in adults don't divide. In these cells, the peripheral nucleoporins are regularly replaced. But what about the scaffold nucleoporins?

To answer this question, cell biologist Martin Hetzer of the Salk Institute for Biological Studies in San Diego, California, and colleagues measured whether nondividing mouse muscle cells replaced scaffold proteins. They didn't. The researchers found similar results in cells from roundworms, which didn't make new scaffold nucleoporins but continued to crank out fresh peripheral nucleoporins. Once the scaffold proteins are in place, they are there for good, the group concludes in tomorrow's issue of Cell.

That means that nuclear pores could accumulate damage during aging. And indeed, the team found that nuclei from old rats allowed in a molecule that was normally too hefty to pass through the pores. In worms, pore leakiness increased after treatment with a compound that induces reactive oxygen species, waste products of metabolism that many researchers suspect cause aging.

Just how leaky pores could contribute to aging is unclear, but one possibility is that certain proteins wander into the nucleus and disrupt gene activity. Leaky pores might also enable proteins from inside the nucleus to escape into the rest of the cell and cause trouble.

"I'm very excited that other people are starting to think about nuclear architecture" and aging, says developmental biologist Jun Liu of Cornell University. But she says more research is necessary to determine if leaky pores cause aging or are a casualty of it. Cell biologist Howard Worman of Columbia University agrees, saying that the key question is whether scientists can connect defective pores "to what the pathologist sees under the microscope in an aged organ or aged tissue."

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