Some of the cells in the body are never replaced across a life span, which leads to forms of system failure and degeneration due to accumulating damage and metabolic waste products not found elsewhere. Interestingly it appears that some of the individual proteins within those cells might not be replaced either. It is unclear as to how much of a long-term challenge that will present once researchers are past the first hurdles in extending healthy human life.
Among these long-lived proteins are those that form nuclear pores, a structure that appears to become damaged in old cells in the nervous system and may contribute to age-related degeneration. Here researchers further investigate, finding that the situation is not as static as first thought:
Most proteins live only two days or less, ensuring that those damaged by inevitable chemical modifications are replaced with new functional copies. [Researchers] have now identified a small subset of proteins in the brain that persist for longer, even more than a year, without being replaced. These long-lived proteins have lifespans significantly longer than the typical protein, and their identification may be relevant to understanding the molecular basis of aging.
The new study [provides] a system-wide identification of proteins with long lifespans in the rat brain, a laboratory model of human biology. The scientists found that long-lived proteins included those involved in gene expression, neuronal cell communication and enzymatic processes, as well as members of the nuclear pore complex (NPC), which is responsible for all traffic into and out of the nucleus. Furthermore, they found that the NPC undergoes slow but finite turnover through the exchange of smaller sub-complexes, not whole NPCs, which may help clear inevitable accumulation of damaged components.
[Researchers] previously found that NPC deterioration might be a general aging mechanism leading to age-related defects in nuclear function. Other laboratories have linked protein homeostasis, or internal stability, to declining cell function and, thus, disease. The new findings reveal cellular components that are at increased risk for damage accumulation, linking long-term protein persistence to the cellular aging process. "Now that we have identified these long-lived proteins, we can begin to examine how they may be affected in aging and what the cell does to compensate for inevitable damage. We're starting to think about how to get functionality back to that younger version of the protein."