The Science of Existence – Longevity


How long a cell may live in a multicellular organism has a lot to do with its function and criticality.

Red blood cells have a 4-month lifespan. They are relatively long-lived service providers.

In contrast, white blood cells – warriors of the immune system – are lucky to last a month. The longest-lived white blood cells are lymphocytes, which retain the memories of past infections, to advise in future conflicts.

Turnover varies tremendously among proteins. Most are replaced several times during a cell’s lifespan. The average protein half-life in a yeast cell is 90 minutes; in mammals, 1–2 days. Only a few proteins last the life of a cell.

There is an intricate accounting system for proteins within cells. Proteins are stochastically festooned with sequential age markers, indicating their service state and degradation to date.

An exception is DNA, which owes its long life to dedicated repair mechanisms that remedy damage. Ordinary proteins lack such support.

The histones that bind DNA are extraordinarily long-lived. These proteins are essential to DNA function, as they act as the spool around which the genetic codes are wound.

Nuclear Pore Complexes

The double-membraned eukaryotic cell nucleus has a selective permeability. Nuclear pores are complexes of large proteins – nucleoporins – which porter various molecules through the nuclear envelope.

A cell may have up to a couple thousand nuclear pore complexes (NPCs), depending upon cell type and life cycle stage. Each NPC has at least 456 nucleoporins, of which there are 30 distinct types. An NPC can conduct 1,000 translocations per complex per second.

This transport includes RNA and ribosomal proteins moving from the nucleus to the cytoplasm; and various proteins, carbohydrates, lipids, and signaling molecules moving into the nucleus. Although smaller molecules simply diffuse through, larger molecules must be recognized and ushered in or out of the nucleus with the help of nucleoporins.

While the turnover of nucleoporins is generally typical of hard-working proteins, scaffold components resist degradation, as the scaffold substructure may hold epigenetic depots critical to transmitting inheritance information. Otherwise, long-lived nucleoporins are those actively involved in translation, which is a later stage in gene expression. These too are mission-critical proteins.

Unlike other large protein complexes, such as ribosomes and proteasomes, an NPC is not replaced in toto. Instead, individual subcomplexes are exchanged at specific intervals. In other words, NPCs undergo regularly scheduled maintenance. Dismantling entire pore complexes might jeopardize the integrity of the nuclear envelope.