What's Your Ageotype?August 13, 2023
What's Your Ageotype?
Ok, I'm not used to manufactured words. Age "o" type is meant to mean there is a typing methodology to how we age. At least, that is the proposal made by Michael Snyder's Genetics team out of Stanford. There is more under the surface.
What this really reveals is the maturing of metabolomics, the methodology Goodenowe pioneered by measuring "everything" in the blood of people as they age. In that process, no one particular item is targeted. Instead, it is accepted that there is a complex interplay between all the items present that changes over time. The key is not one measure but measurements over time with different outcomes revealing themselves by the nature of the changes revealed. This process reverses the methodology of science and medicine. The old-fashioned way, what we deem as traditional medicine, you could call "top-down". You identify an illness or a symptom and study that symptom/illness to identify everything your imagination can find about it. For example, with tuberculosis, we culture the bacteria and find its sensitivity. We take X-rays and CT scans to see what organs may be involved. You are used to all that. That's how the house of medicine "works up" an illness.
Metabolomics is "bottom-up". There is no target and no disease being studied. Everything is being studied. This creates massive databases and requires huge computing power to process. And, at the end of the day, detailed statistical analysis. From that, magic emerges. Patterns not seen by any other method are revealed. Instead of questions looking for an answer, we have answers looking for a question.
What Dr. Snyder did was to take 106 individuals, ages 29 to 75, and follow them longitudinally. Their primary focus was to assess the risk of prediabetes and metabolic syndrome's effect on aging. Despite aging being a huge topic of interest, we really don't know much about how it happens. In this study, subjects were followed between 3-4 years of time with quarterly visits and assessments. Proteomics (every protein measurable), metabolomics on plasma samples, transcriptome analysis on mononuclear cells, targeted cytokine assays using serum, nasal and gut microbiome analysis using 16S rRNA sequencing, exome sequencing (measuring all the circulating messenger RNA), and 51 clinical lab tests were acquired on each visit. There were 18 million data points to analyze. Even in that small time frame, and with that small a group of people aged that far apart....seemingly random and not much in common....some very interesting patterns emerged.
The team found 608 distinct molecules, bacteria, and genes that changed significantly over just four years. Those changes occurred in four distinct patterns associated with four organ systems - kidneys, liver, immune, and "general". Most of the subjects aged along all four pathways, with one predominating. Some had two more dominant. Like an aging car, the whole gets older together but some parts actually wear out faster.
What this really offers are possible new insights into how we address aging. If you are a "kidney ager" you may well benefit from more water. A liver ager would do well to lay off alcohol and Tylenol. A metabolic ager needs to lose weight more urgently than others.
There are probably more patterns and types to be revealed. This may be a valid means of identifying risk, or not. Some of the subjects in this study improved their markers of aging by losing weight, drinking more water, or whatever. Are those efforts statistically valid? Time will tell. It does reveal that bottom-up science is a new field that is revealing a new method of looking at ourselves. As it matures we will find insights we haven't seen before.
www.What will Work for me? Good science starts by asking a question, or a hypothesis, and goes looking for an answer, which always leads to more questions. When you do it "backward" and gather all the answers, you go looking for all the answers and then ask the questions. We will have to learn that "good science always leads to more answers", so what are the questions? What do I need to do for now? I have problematic diabetes genes. That I know. Losing weight and keeping it off is a devil. This test isn't available publically, nor is it mature enough to use in that fashion. Goodenowe, who measured 25,000 items in a cohort of 1,500 aging Catholic clergy discovered plasmalogens with this method. I think more discoveries are waiting in the wings. I'm taking my plasmalogens.
References: Natural Medicine ,
1. What is metabolomics? Answer: The measurement of "everything you can find" in someone's blood. The metabolome is what your metabolic processes make.
2. How is the metabolome different from the genome? Answer: Your genome is your genetic code. That's your hard wiring. Your metabolome is what your genes make after being read and interacting with your environment.
3. What is your "exome"? Answer: For another day. That is the reading of all your circulating mRNA carried in exosomes. Your circulating mRNA reflects the DNA that has been activated. You have read about it recently regarding COVID as it has been used to reveal the activity of your COVID response. (Research so far.) You could argue that your exome is halfway between your genome and metabolome.
4. What is your biome? Answer: At 100-1000 times the amount of genetic diversity over you, your biome is all the bacteria living in you. We have recently learned that the biome of your tongue is distinct and tasked with making nitric oxide. Your gut biome is a critical component of your healthy self. When you are full of it, that's a good thing!
5. Can you test for your Age-o-type. Answer: Not yet, and maybe never. Let's watch and wait.