What do redwoods, quahog clams, Greenland sharks, bowhead whales, and Galapagos tortoises have in common? Although this sounds like a riddle that could keep the greatest of philosophers up at night, the answer is quite simple: These organisms are among the longest-lived on the planet. While these organisms will outlive us by hundreds to thousands of years, we still have many things in common, including the need to regularly replenish the proteins we make (and which make us).
Not all proteins need to be replenished at the same rate. Some proteins quickly disappear almost the same moment they are created, but others have the potential to linger for centuries. Interest in these long-lasting proteins (LLPs) has spawned a new field of study (reviewed in (Truscott, Schey, & Friedrich, 2016)).
Where in the body do LLPs exist? One of the first LLPs that may pop into a person’s mind is keratin found in hair or fur. Even if removed from a fur/hair-bearing creature or if the creature dies, keratin can last for a millennia or more in the right conditions (mammoths and other ice age creatures have been discovered still bearing their fur). Aside from our exterior, LLPs can be found throughout our bodies. Research has shown that LLPs exist in the eyes, muscles, oocytes, bones, lungs, heart, liver and teeth. Surprisingly, the brain has the most diverse and most identified LLPs.
Just because LLPs can stick around for a long time does not mean that they maintain their original form. Just like automobiles are susceptible to rust and fading, LLPs too can succumb to changes as they age. These changes include a buildup of post-translational modifications (chemical compounds added or removed from the protein), enzymatic digestion, or spontaneous degradation. Though the LLPs are altered, these modified or truncated versions may be stable and detectable for a long time.
The build-up of modified LLPs may be related to many age-related diseases. In the eyes, LLPs have been implicated in many age-related problems, such as cataracts. For other instances, the field is still new, but evidence is mounting. Take amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease as example cases. Both typically occur later in life. In the ALS field, it has been hypothesized that malfunctioning cellular components, which happen to be LLPs, are degrading with age and may contribute to the patients’ deterioration. In Alzheimer’s disease, the brain ravaging plaques contain LLPs that have been spontaneously modified over the years. This toxic build-up could be an underwriting cause for the manifesting symptoms.
Aside from the toxic build-up being a likely root cause of ailments, the build-up of modified LLPs could be the underpinning for other disorders too. For instance, modifications to proteins, such as LLPs, can elicit an immune response. This has been observed for proteins associated with rheumatoid arthritis, lupus erythematosis and potentially multiple sclerosis.
While it may seem that organisms are at the mercy of the changes that can befall LLPs, research shows that mechanisms do exist that can undo some of the age-related changes. However, the specific mechanisms for restoration of LLPs remains unknown. But it is clear the LLPs are bringing a new dimension to the discovery and understanding of disease biomarkers in addition to revealing yet another facet of the complexity of biology.
Truscott, R. J., Schey, K. L., & Friedrich, M. G. (2016). Old Proteins in Man: A Field in its Infancy. Trends Biochem Sci, 41(8), 654-664. doi:10.1016/j.tibs.2016.06.004