Longevity Briefs: Why Do Some People Live To 100? The Quality Of Their Proteins May Be Key

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Though centenarians – people who have lived to age 100 – are on the rise, they’re still pretty rare. In Europe, only around 1 in 5000 people are centenarians. These people clearly age more successfully than others, but why? Answering this question could help us target the ageing process more effectively.

Proteins are biology’s functional molecules – they control the flow of other molecules across cell membranes, contract your muscles, and deliver molecular messages. Cells build their own proteins according to instructions found in the genetic code, but this process is not 100% faithful and can go wrong. Proteins may also fold incorrectly or become damaged after they have been made. Cells have various ‘quality control’ systems to prevent these errors and remove dysfunctional proteins, but these systems tend to fail in advanced age.

What did the researchers do: In this article, researchers review what we know about protein production and quality control in centenarians in comparison to normally-ageing people. Do centenarians have a ‘younger’ protein set than might be expected and, if so, why?

Key takeaway(s) from this research: There is evidence to suggest that centenarians’ protein biology operates like that of a more youthful person in multiple ways:

• Centenarians have more gene variants associated with maintaining and repairing the DNA itself. This in turn leads to healthier proteins and healthier ribosomes (the structures responsible for protein assembly).
• Centenarians accumulate epigenetic changes at a slower rate than average overall. They may also accumulate additional, beneficial epigenetic modifications that reduce the activity of genes associated with age-related disease.
• Centenarians have altered activity of molecules that control how cells ‘spend’ their energy, generally leading to lower energy consumption.
• After proteins are constructed, they receive additional modifications (called post-translational modifications). In centenarians, certain types of modifications are particularly enhanced, which might contribute to reduced levels of inflammation.
• Centenarians retain an ability to degrade faulty proteins similar to that of much younger individuals.

The authors argue that a key difference between centenarians and those who fail to reach age 100 is that centenarians retain a healthy, balanced composition of well-functioning proteins. Most people suffer a decline in the fidelity of protein production, while faulty proteins are not effectively removed in old age.

These differences are partly genetic and partly environmental. Proteins and the systems that regulate them can be damaged by various stressors and insults such as free radicals – molecules that steal electrons off other molecules. It’s possible that maintaining a healthy protein production and quality control requires you to be exposed to just the right amount of these stressors – enough to stimulate cells’ defensive systems without overloading them. As for drugs, scientists are already investigating compounds that target some of the systems described above. Rapamycin and metformin for example, perhaps the two most promising drugs with ‘anti ageing’ potential, both affect how cells handle their energy.