Proteins Matter… (and no, I’m not talking about “Whey” protein)
Hallmark of Aging #4:
Loss of Proteostasis
Proteins are the building blocks of life. Without them, we wouldn't be able to breathe, move, or think. In this post, I'm going to talk about the 4th "Hallmark of Aging," the loss of proteostasis. Proteostasis is our bodies ability to control its levels of proteins and to create new proteins when needed. As we get older, our cells lose this ability to synthesize and regulate proteins properly. This can lead to all sorts of health problems, as proteins are essential for cellular function in all tissue types. Luckily, new research is emerging on ways to prevent the loss of proteostasis and keep our cells healthy as we age.
Proteostasis is essential for maintaining strong health and extending longevity. Proteins are responsible for many essential tasks inside of cells, such as transporting molecules, maintaining cell shape, among countless other functions. When proteostasis is lost, proteins and cells can become damaged and dysfunctional. This can lead to a wide range of health problems as we age. The two essential functions of proteostasis that deteriorate as humans age are: 1) Regulation, or clearing out dysfunctional proteins, 2) Synthesis, or building new proteins to replace the old, damaged ones.
There are a number of new research and technologies being discovered to support proteostasis. For example, scientists are studying the effects of caloric restriction and fasting on proteostasis, and investigating ways to boost protein synthesis. There are also new drugs and therapies in development that aim to improve proteostasis function. There are countless companies with drug candidates that have compounds affecting proteostasis in some way, so we are sure to see breakthroughs, especially in relation to specific diseases. Some key scientists researching proteostasis include David Sinclair from Harvard Medical School and Valter Longo from the University of Southern California, but there are a multitude of researchers working on these critical scientific discoveries.
An insightful example of the harm that losing proteostasis can cause are neurodegnerative diseases such as Alzheimer's disease. Scientists still do not have certainty on the exact biological forces that cascade into Alzheimer's disease. The amyloid hypothesis is the leading theory on what causes Alzheimer's disease, but the exact role of amyloid proteins in the development of the disease is still uncertain. Whether dysfunctional amyloid proteins are the primary cause or a different combination of unidentified proteins causes Alzheimer's, we can have strong confidence that, generally, the loss of proteostasis plays a huge role in this debilitating disease. For example, scientists know that the characteristic plaques and tau tangles seen in the brain tissue of Alzheimer's patients are clumps of damaged proteins. This is just one example of how important proteostasis is for human health, and how its deterioration can lead to aging.
This Alzheimer's example also illustrates the immense quantity of biological questions without answers. We know that clumps of damaged proteins are seen in Alzheimer's patients, but we do not have consensus on the exact biological interactions that cause the damage.
Are we getting closer to answers to the most complex of biological conundrums such as Alzheimer's? Most definitely. New research tools that have emerged over the last decade are unlocking biological knowledge like never before. This tsunami of new biological data in the form of genomics (DNA data), transcriptomics (RNA data), proteomics (protein data), and many other data sources. Each of these data sources separately will deserve many future blog posts, so I will spare the details now. Analyzing these "omics" data sources together has created the field known as "Multi-Omics." We are already seeing initial breakthroughs that are likely to accelerate knowledge and therapeutic progress.
Scientists are making remarkable progress in understanding proteostasis and its role in aging. The downstream implications of new research tools and techniques are only just beginning to unlock new treasure troves of actionable biological insight. I have confidence that the development of precise therapeutics that target novel pathways related to declining proteostasis will only accelerate as our technologies and data analysis capabilities mature. We can be confident that these advances will have a profound impact on human health as we age. That said, even simple healthy lifestyle habits are likely to make a substantial impact on maintaining proteostasis. As author and futurist Ray Kurzweil would say, perhaps we just need implement the good habits today to "live long enough to live forever."