What Marsupials Tell Us About Human Pregnancy

What Marsupials Tell Us About Human Pregnancy

With pregnancy comes not just new life, but also the collection of huge amounts of data and numerous doctor visits to ensure the health of the mother and child. The pregnant body undergoes myriad biological changes that can give rise to problems that yield a bad result that all involved want to avoid.

A whole cottage industry of direct-to-consumer (DTC) products/services has sprung up, aimed at providing peace-of-mind health information between doctor visits. However, many of these products are likely having the opposite effect, creating more anxiety, more doctor visits and more unnecessary medical care (Thielking, 2019). Although the direction of prenatal care is toward greater empowerment of the mother and her supporters, the technology at hand (and the data it provides) is simply not yet good enough to have a positive rather than negative impact.

What data/technology should we be pursuing? A recent study in marsupials aimed at understanding how embryo implantation evolved provides a hint (Griffith et al., 2017). The research team noted that the implantation event appears to modify the normal inflammation response to a foreign body. The group suggests that this could explain the increased risk of miscarriage if a person is on anti-inflammatory medication during the implantation phase.

Griffith et al. further compared the gestation styles of marsupials and humans. Both humans and marsupials rely on inflammation for embryo implantation and for birth. Unlike marsupials, in which the newborn crawls into a pouch for further development to avoid the mother’s immune system, humans and other placental mammals do something different. After implantation, these creatures mount an anti-inflammation response until it is time to give birth. This gives the embryo time to mature and not be attacked by the mother’s immune system.

Monitoring the “on-off-on” cycling of the inflammatory response could be a great way to see how well the pregnancy is going and get early warning of problems from a mistimed immune response. (Also, this could be the sought-after answer to the question mentioned above.) One group is already on top of that and used the insightful SomaLogic® technology along with other information to monitor what happens to the immune system during the course of a pregnancy (Aghaeepour et al., 2017). Although the sample size was small, the group’s findings lay the groundwork for understanding what happens to the immune system during a healthy pregnancy in great detail. It could open the door to the possibility of new diagnostics to determine if a pregnant individual is at risk of problems with the pregnancy. It might be enough to put many worried minds at ease and reduce unnecessary doctor visits. Perhaps, it could even reduce the workload of practioners. Indeed, it might even revolutionize the field.

 

References

Aghaeepour, N., Ganio, E. A., McIlwain, D., Tsai, A. S., Tingle, M., Van Gassen, S., . . . Gaudilliere, B. (2017). An immune clock of human pregnancy. Sci Immunol, 2(15). doi:10.1126/sciimmunol.aan2946

Griffith, O. W., Chavan, A. R., Protopapas, S., Maziarz, J., Romero, R., & Wagner, G. P. (2017). Embryo implantation evolved from an ancestral inflammatory attachment reaction. Proc Natl Acad Sci U S A, 114(32), E6566-E6575. doi:10.1073/pnas.1701129114

Thielking, M. (2019, July 23) As pregnancy tech proliferates, women and their doctors wade through what’s helpful — and what’s a headache. STAT. Retrieved on August 5, 2019 from https://www.statnews.com/2019/07/23/pregnancy-tech-help-headache/.

 

Redefining Middle Age

Redefining Middle Age

Depending on your preferred authority, “middle age” begins at 40 or 45, and ends 20 years later at the beginning of “old age.” These years are a time of transition across the population, particularly in physical status. But what if an individual’s proteins offer a different take on the meaning of middle age (and even old age)?

Recently, an international team reported in Nature Medicine that how we view middle age is likely wrong (Lehallier et al., 2019). Using the SomaLogic technology, they looked at changes in thousands of circulating proteins among 4,263 healthy adults, spanning the ages of 18 to 95 years old. In digging through all those proteins, they uncovered a “proteomic clock” that marks the passage of biological time. Specifically, the team identified three events that happen in adulthood. The first aging event happens around 34 years of age. The second one occurs at 60 years of age, which was termed “middle age” by the authors. And the third one appears at 78 years of age, heralding the start of “old age.”

The researchers noted other fascinating phenomena. For example, their work confirms previous suggestions that people can be biologically younger than the age stated on their identification card. They also noted that people who performed well on cognitive and physical tests tended to age slower according to their protein profiles, and that women aged slower than men.

On the flip side, the researchers found that it is also possible to age faster. For example, the protein patterns in people with Alzheimer’s disease or Downs Syndrome resembled the patterns associated with the proteome of older people, which could help explain the rapid aging seen in these disorders.

So, perhaps 40 or 45 are not really middle age and 60 or 65 even are not old – at least from a biological perspective! A lovely thought one can have even if your birthday cake is highly illuminated.

References

Lehallier, B., Gate, D., Schaum, N., Nanasi, T., Lee, S. E., Yousef, H., . . . Wyss-Coray, T. (2019). Undulating changes in human plasma proteome profiles across the lifespan. Nat Med, 25(12), 1843-1850. doi:10.1038/s41591-019-0673-2

Longing for Home and Better Outcomes

Longing for Home and Better Outcomes

Poor guy. Since he was little, we knew he had the lungs of a whale. His cries reaffirmed this talent, echoing down the halls. He wants to go home, NOW! Yes, Noodle B. was not enjoying his medical visit. I also knew he would not be a happy camper if he needed another surgery. You see, our elderly furry head-of-the-household does not have the best post-operative experiences. However, I did not know, until recently, that he has that post-op issue in common with many humans.

As we get older, our ability to bounce back quickly from non-emergency surgeries diminishes (Gajdos et al., 2013). This can result in numerous complications and longer stays in the hospital rather than going to recover in the comfort of home. Although chronological age (not our true biological age) might help assess risk for surgery, is there something better?

A research group sought to answer that question by looking at protein changes and post-operative experiences (Fong et al., 2019). From blood samples of people from the Successful Aging after Elective Surgery (SAGES) study, the team looked for changes in protein levels using SomaLogic® technology. After surgeries, the team noted 43% of the proteins analyzed showed significant changes from the pre-operation levels, some of which were not found in other studies. From their analysis, changes in protein levels could potentially be explained by changes in levels of regulating proteins upstream in the cascade of signaling events, such as pro-inflammatory cytokines.

So, did they identify a new way to identify a patient needing more time in the hospital after a surgery or being discharged to a post-acute facility? From the small study, the team did find encouraging – but not definitive – results. One protein in particular, IL-6, showed that its levels prior to surgery could be a good indication that the patient will need more time in the hospital. After surgery, IL-6 and several other proteins appear to offer an early alarm of problems and the need to be discharged to a post-acute facility.

It is encouraging to think that the medical community is on the cusp of having new tests that may help surgeons and other medical care staff better stratify and plan human post-op care. Maybe someday it will even lead to help for Noodle B and his kin.

References
Fong, T. G., Chan, N. Y., Dillon, S. T., Zhou, W., Tripp, B., Ngo, L. H., . . . Libermann, T. A. (2019). Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan. Ann Surg. doi:10.1097/SLA.0000000000003283

Gajdos, C., Kile, D., Hawn, M. T., Finlayson, E., Henderson, W. G., & Robinson, T. N. (2013). Advancing age and 30-day adverse outcomes after nonemergent general surgeries. J Am Geriatr Soc, 61(9), 1608-1614. doi:10.1111/jgs.12401

 

What are Proteins? Chopped Liver?

What are Proteins? Chopped Liver?


By Laura Mizoue

You’ve heard of insulin, right? You probably know that it helps regulate blood sugar, that its levels rise and fall depending on what and when you eat, and that a lot of diabetics have to inject themselves with it. But did you know that insulin is a protein?

Proteins have a serious branding problem. Say “protein” and most people think chicken or beef. Say “protein molecule” and it draws a blank stare. This presents a real problem when you’re trying to explain the value of measuring thousands of proteins in a person’s blood. And the maddening part is that most people already know how important insulin, hemoglobin, collagen, growth hormone, liver enzymes, inflammation markers and clotting factors are, they just don’t know that they’re proteins.

Because there are so many different proteins (molecules) in the human body — approximately 20,000 — and they do so many completely different things, proteins are never called proteins. In fact, proteins go by a host of monikers — enzymes, hormones, antibodies, regulators, receptors, transporters, signaling molecules — pretty much anything except the word “protein.”

Of all the names that proteins are called, the one that’s the most misleading is “gene expression product” because it implies that genes are where the action is. But opioids, statins, NSAIDs, SSRIs, ACE inhibitors and almost all other pharmaceutical drugs don’t target genes, they target proteins.

Whenever genomic testing companies want you to “meet your genes” what they really want you to do is meet your proteins. This is because your proteins, not your static pieces of DNA, are the molecules that actually do the work to keep you alive and well. If a mutation in a gene is associated with disease, it’s usually because it results in a defective protein that can’t do its job effectively or a protein that doesn’t even show up to work.

And they’re important jobs: stabilizing your blood sugar, transporting oxygen, helping you move, regulating your mood, fighting infection. Sometimes your body can get by for a while, but over time, if all your protein players aren’t working together in a coordinated fashion, the work situation breaks down and bad things can happen.

At SomaLogic, we measure the levels of approximately 5000 human proteins from a single blood sample. We believe that proteins directly reflect what’s going on in the human body and can help predict what’s going to happen in the future.

So let’s tell it like it is and call a protein a protein.

 

Dynamic Data for a Dynamic You

Dynamic Data for a Dynamic You

Do you know how many different hats you wear in a day? Think about all the different roles you may take on during the course of the day – parent, significant other, boss, employee, cook, cleaner, accountant, household zookeeper, negotiator, etc. The number of roles can seem endless, but they reflect just how “dynamic” you can be and have to be. Like you, life is, indeed, dynamic. Including our health, especially how it changes over time. The question is what data will help – static or dynamic data – in managing your health?

What would static data be? Well, your genetic code that you were born with could count as static for the most part. For those of us growing up in the post-Human-Genome-Project world, it has been drummed into our heads – hyped even – that our genes define us. By examining our DNA (the body’s equivalent to the 0’s and 1’s used to create software, such as genes), we can see what our health future has in store. But what if you are dealt a dreadful set of gene cards? Fortunately, we have learned enough now to know that you are not out of luck: We now know that genes do not dictate fate in the vast majority of cases.

Also, sequencing your genome (all the DNA stuff you inherit) may not accurately describe your complete genetic portrait. You may in fact have more than one genome residing in your body for a variety of reasons which, in addition to just the regular errors associated with DNA sequencing at scale, could compromise the accuracy of any conclusions drawn.

However, even if you had your complete and error-free genetic report in hand, interpreting what it means with regards to health is still uncertain. Turns out that a single mutation (i.e., variation) rarely means you will get “x” disease or condition. In fact, research has shown that variants found in 11,544 genes to be associated with at least one of 518 traits (Watanabe et al., 2019). So, thousands of genes may have influence on a single trait.

Now, let’s examine dynamic data. A wonderful example would be proteomic (all your proteins) data. Proteins are the products of your genes. Yet, how much or little a protein exists can be influenced by so many factors and change throughout the day, etc.

At SomaLogic, we have worked for 20 years to develop the technology to monitor the rise and fall of protein levels and understand how those reflect a tremendous amount of detail about your multi-tasking body and your health. In fact, these fluctuations have generated so much information that hundreds of papers have been written, with many more yet to appear. From the bounty, we see just how protein information might help with arthritis, alert patients about an impending early demise or a non-ideal surgery outcome (Fong et al., 2019), foretell possible failure of a clinical trial (Williams et al., 2018), provide a better alert than traditional “gold standards” regarding a cardiovascular event (Ganz et al., 2016), etc. Protein information could even tell how your body responds to a diet (Thrush et al., 2018) or how exercise is affecting it (Santos-Parker, Santos-Parker, McQueen, Martens, & Seals, 2018).

Let’s get back to our question. What data are as dynamic as you? The answer lies in your proteins. Knowing your protein changes and how to optimize them could help you more effectively meet all the demands of your many different roles.

 

References

Fong, T. G., Chan, N. Y., Dillon, S. T., Zhou, W., Tripp, B., Ngo, L. H., . . . Libermann, T. A. (2019). Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan. Ann Surg. doi:10.1097/SLA.0000000000003283

Ganz, P., Heidecker, B., Hveem, K., Jonasson, C., Kato, S., Segal, M. R., . . . Williams, S. A. (2016). Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients With Stable Coronary Heart Disease. JAMA, 315(23), 2532-2541. doi:10.1001/jama.2016.5951

Santos-Parker, J. R., Santos-Parker, K. S., McQueen, M. B., Martens, C. R., & Seals, D. R. (2018). Habitual Aerobic Exercise and Circulating Proteomic Patterns in Healthy Adults: Relation to Indicators of Healthspan. J Appl Physiol (1985). doi:10.1152/japplphysiol.00458.2018

Thrush, A. B., Antoun, G., Nikpay, M., Patten, D. A., DeVlugt, C., Mauger, J. F., . . . Harper, M. E. (2018). Diet-resistant obesity is characterized by a distinct plasma proteomic signature and impaired muscle fiber metabolism. Int J Obes (Lond), 42(3), 353-362. doi:10.1038/ijo.2017.286

Watanabe, K., Stringer, S., Frei, O., Umicevic Mirkov, M., de Leeuw, C., Polderman, T. J. C., . . . Posthuma, D. (2019). A global overview of pleiotropy and genetic architecture in complex traits. Nat Genet. doi:10.1038/s41588-019-0481-0

Williams, S. A., Murthy, A. C., DeLisle, R. K., Hyde, C., Malarstig, A., Ostroff, R., . . . Ganz, P. (2018). Improving Assessment of Drug Safety Through Proteomics: Early Detection and Mechanistic Characterization of the Unforeseen Harmful Effects of Torcetrapib. Circulation, 137(10), 999-1010. doi:10.1161/CIRCULATIONAHA.117.028213

 

Detecting Alzheimer’s Disease Before Being Erased Away

Detecting Alzheimer’s Disease Before Being Erased Away

Another forgetful moment…Keys found in fridge…Was it just due to it being Monday, to a poor night’s sleep or could it be something more alarming? Events such as these can raise the hairs on most people’s necks. If it turns out to be something worse than just sleep-deprivation, such as Alzheimer’s disease (AD), the person and loved ones may be in for rough and expensive ride lasting decades as the afflicted brain – and its memories and functions – is erased.

AD comes in two forms, early-onset or late-onset, and both produce a range of symptoms from mild to severe (NIA, 2019a). At first, the disease may just manifest in ways that only the person or loved ones may notice – repeating questions, getting lost, putting stuff in odd places (e.g., keys in the fridge), etc. As the disease progresses, cognitive ability gets worse. People may no longer recognize loved ones, hallucinate, and have difficulty carrying out everyday tasks. In the most severe form, the disease essentially erases the person mentally and severs the person’s control of their body. Often towards the end, they lose the ability to swallow, leading to pneumonia and death.

What exactly is happening to the brain that could ultimately erase a person? In a nutshell, the brain is shrinking – considerably. The science is not entirely clear about what is exactly happening, but the data suggests two proteins, amyloid and tau, are at the epicenter (NIA, 2019b). Proteins start to form “plaques” and “tangles,” eventually cutting off neurons from one another. Separated, the cells die, which contributes to the shrinkage and erasure.

The shrinkage does not happen instantaneously, but rather over years to decades. Current methods to diagnose AD include spinal taps, MRI or PET imaging, but may not be sensitive enough to catch early stages or to stratify patients in an optimal way to truly benefit clinical trials of promising treatments (Shi et al., 2019).

Looking at changes in our proteins might be another approach worth trying. In a study with the largest sample size known to date surveying the most proteins possible, a team of researchers went looking for new insights (Shi et al., 2019). Although their work is preliminary, proteomics appears to deliver both better understanding the biology and improvement in ways to treat AD. In their study, they identified ten molecular pathways as markedly changed in AD patients, including some already suspected. Furthermore, the inclusion of protein data improved AD vs. non-AD patient sorting over just using genetic information and age.

A test that can screen accurately for AD and do so better than current tests would be a huge step forward for diagnosing the disease, maybe even pre-symptomatically. At that point, the question becomes: If such a test existed, would you take it? The answer depends, in part, on how soon effective treatments can be found. Perhaps using these same findings will get us there faster too.

 

References

National Institute of Aging (NIA) (2019a). What Are the Signs of Alzheimer’s Disease? Retrieved on September 10, 2019 from https://www.nia.nih.gov/health/what-are-signs-alzheimers-disease.

National Institute of Aging (NIA) (2019b). Video: How Alzheimer’s Changes the Brain. Retrieved on September 17, 2019 from https://www.nia.nih.gov/health/video-how-alzheimers-changes-brain?utm_source=ADvideo&utm_medium=web&utm_campaign=rightrail.

Shi, L., Westwood, S., Baird, A. L., Winchester, L., Dobricic, V., Kilpert, F., . . . Nevado-Holgado, A. J. (2019). Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay. Alzheimers Dement. doi:10.1016/j.jalz.2019.06.4951