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When it comes to the discussion of longevity and aging, you’re no doubt familiar with the so-called Blue Zones¹ – environments in which unique characteristics and lifestyles seem to produce the world’s longest-lived people. Elements such as high intake of wild plants, absence of smoking, legume intake, conscientiousness, gratitude, tannin-rich beverages and a handful of other qualitative markers are associated with these zones. And while these markers are indeed valuable subjective measurements of longevity or risk of mortality, I’m a fan of combining such measurements with quantitative, objective data and biomarkers that truly allow one to marry ancestral wisdom with modern science.

As you may know, there are specific physiological biomarkers that occur in the human body that can predict how long you will live. Most such biomarkers are not even glanced at during your standard checkup at the doctor, but fortunately, WellnessFX can now measure most of these biomarkers with the new Greenfield Anti-Aging Biomarkers Lab Testing². If you care at all about how well you’re doing in the longevity game, you’re curious how fast you’re aging, or you want to measure the efficacy of your anti-aging efforts, it’s worth paying attention to each of these parameters that I and the team at WellnessFX have personally selected to give you the biggest bang for your buck in the anti-aging department.

The 10 Best Anti-Aging Biomarkers To Test

1. RBC Magnesium

Red blood cell (RBC) magnesium is a mineral that can help predict important longevity markers such as insulin sensitivity³ and likelihood to be hospitalized⁴whereas high levels of RBC magnesium can predict physical performance and potential for sarcopenia (muscle-wasting⁵ as you age.

An RBC magnesium test can provide an earlier indicator of magnesium deficiency than a standard magnesium blood test. This is because when levels are low, the body will pull magnesium from the cells to keep blood levels normal. In this case a magnesium blood test may show normal levels while an RBC magnesium test will give a far more accurate result.

2. Estradiol

During the first year of menopause, women lose on average 80% per year of their estrogens!⁶ This can result in a significantly accelerated decline in muscle mass and strength. Related to this loss of estrogens⁷, which can of course cause subsequent decreases in physical function and the ability to be spry and supple⁸ as you age. Higher endogenous estrogen levels are associated with higher muscle strength⁹ and lower rates of fall-related limb fractures even after adjusting for bone mineral density¹⁰. Estrogens can also stimulate muscle repair and regenerative processes¹¹, probably by acting as an antioxidant¹², thus limiting oxidative damage¹³; acting as a membrane stabilizer by interacting with cell membrane phospholipids, and binding to estrogen receptors to govern regulation of a number of downstream genes and molecular targets¹⁴.

Estrogens also play a protective role against oxidative stress protection¹⁵, and can participate in the antioxidant system because they can decrease the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an important source of superoxide radical, and can increase nitric oxide (NO) availability¹⁶. In addition, estradiol activates mitogen-activated protein kinase and nuclear factor-κB signaling after binding to the estrogen receptor, and this stimulates the expression of mitochondrial antioxidant enzymes such as manganese superoxide dismutase and glutathione peroxidase, which results in reduced reactive oxygen species production of mitochondria (possibly contributing to the longer expected lifespan of women compared with men).

Estrogens also play a key role in the regulation of bone mass¹⁷ and strength by controlling the activity of bone-forming osteoblasts and inhibiting activity of bone-resorbing osteoclasts. Bone tissue is essential for structural support and locomotion in the vertebrae and critical for hematopoiesis (red blood cell production) as one ages. Bones also serve as an endocrine organ in the regulation of calcium homeostasis¹⁸. Interestingly, when women are treated with exogenous estrogens, the decrease in bone mass and increase in bone turnover can be reversed, suggesting that estrogens have a potent bone protective effect¹⁹. Here’s a great resource to see optimal estrogen (and testosterone) levels in men and women²⁰.

3. High-sensitivity C-reactive protein

Over two dozen research studies²¹ have proven that baseline levels of the inflammatory marker C-reactive protein (CRP) in healthy men and women are highly predictive of future risk of cardiovascular ailments – including heart attack, diabetes, stroke, sudden cardiac death, and the development of peripheral arterial disease.

It has also been shown²² that CRP levels predict repeat coronary events among patients who already suffer from heart disease and that the outcome of patients immediately after a heart attack is tightly linked to CRP levels. Ultimately, individuals with excessive levels of CRP have a risk about two to three times higher than the risk of those with low, optimal levels.

As you can read more about in WellnessFX’s article “High-Sensitivity C-Reactive Protein – A Beacon for Inflammation”²³, it’s been said that the CRP test, combined with a basic lipid panel (also included on this anti-aging panel) is the single, best way to evaluate your risk of heart disease. By eating a diet high in anti-inflammatory herbs, spices, and nutrients (especially turmeric and fish oil) and avoiding overtraining and excessive stress and toxin exposure, I personally try to keep my CRP below 0.5 and prefer to have it below 0.2.

4. Triglyceride:HDL Ratio

Also known as the “atherogenic index of plasma” (yep, that’s a mouthful), a high triglyceride:HDL ratio (meaning a high number of triglycerides relative to your HDL cholesterol) is also one of the best indicators of your risk for heart disease. This test also has the added benefit of also predicting lipoprotein particle size²⁴ and insulin resistance²⁵, two other important markers for longevity. For example, in one study in elderly women, the triglyceride:HDL ratio predicted all-cause mortality²⁶ (not only cardiovascular mortality, but overall risk of dying from anything!).

There are of course a host of additional studies²⁷ on this ratio, including this²⁸ study that shows triglyceride/HDL ratio predicts coronary heart disease and cardiovascular disease risk mortality as well as or better than does full blown metabolic syndrome. A ratio of 2 or under is good for your triglyceride:HDL ratio, and I’m a bigger fan of shooting for 1 or under. Above 4 is bad news bears.

5 & 6. Full Lipid Panel And Omega 3 Fatty Acids

An advanced cardiovascular and lipid panel²⁹ goes beyond the typical cholesterol test to help uncover early risk factors for heart disease. Most people may not realize it, but a cholesterol test is important way before you feel old or sick. A basic lipid panel measures fats and fatty substances in the blood that indicate current and potential heart health, such as LDL, HDL, triglycerides and total cholesterol, while a full lipid panel goes far and beyond typical blood tests, and includes a particle size measurement.

Particle size is extraordinarily important, because research has shown³⁰ that small dense LDL cholesterol can be inflammatory and toxic to blood vessels, and that a high level of Lipoprotein(a) indicates the most dangerous blood lipids. This Lp(a) is a specific type of small LDL cholesterol particle that inflames your blood and makes it “sticky”, and patients with Lp(a) are more prone to clotting. A comprehensive lipid panel can investigate the types of cholesterol particles in your blood and give you a far more accurate profile of your cardiovascular risk than standard cholesterol tests do.

In addition, the fatty acids present in your blood are worth examining because a higher proportion of omega-6 linoleic acid can result in lower longevity and predict earlier death and physical and cognitive decline. This is because linoleic acid can make red blood cells more susceptible to oxidative damage, which ages the the cells³¹ and impairs their ability to deliver oxygen. In contrast, the more omega-3 fatty acid in the red blood cells, the lower your risk for colon cancer (and the higher the omega-6, the higher the risk for colon cancer).³² Older individuals with low levels of omega-3 fatty acids physically decline more quickly³³ than older adults with higher levels. Low omega-3 fatty acid count also predicts smaller brain volume and cognitive decline³⁴, even in older adults who don’t possess any other symptoms of dementia.

Known as the saturation index, your stearic acid:oleic acid ratio is another important marker to check. Stearic acid is a saturated fat and oleic acid is a monounsaturated fat. A lower saturation index is linked to several aging-related diseases, including non-alcoholic fatty liver disease³⁵, prostate cancer³⁶, colon cancer³⁷ and gallbladder cancer³⁸. When it comes to longevity, a higher amount of stearic acid is preferred.

7. Testosterone + Free Testosterone

Several reports published in medical literature have proven that low testosterone is associated with increased mortality. They include this study³⁹, which shows that low testosterone levels are associated with increased mortality in male veterans; this study⁴⁰, which shows that low testosterone is associated with increased mortality over a 20 year time span, independent of metabolic syndrome, diabetes, and prevalent cardiovascular disease (but attenuated by adjustment for IL-6 and C-reactive protein, making yet another case for keeping your inflammation low, especially if you have lower testosterone); and this report⁴¹, which concludes that low testosterone may be even more dangerous than previously thought, and lead to a greater risk of death.

In that final report, men with low testosterone had a 33% greater death risk over their next 18 years of life compared with men who had higher testosterone. The study tracked nearly 800 men, 50 to 91 years old, living in California. Their testosterone level was measured at the beginning of the study, and their health was then tracked over the next 20 years. In addition, low testosterone can also drastically affect the quality of your life as you age, as symptoms reported by these men included decreased libido, erectile dysfunction, fatigue, loss of strength, decrease in bone density and decreased muscle mass. Also, these men tended to be overweight or obese, and at higher risk for cardiovascular disease and diabetes. Men with the lowest testosterone, below 241 total serum level, were 40% more likely to die!

You can delve into even more resources on the link between testosterone and longevity in this helpful article by Dr. Jeffrey Dach⁴², which includes links to optimal testosterone levels.

8. IGF-1 (Growth hormone surrogate)

I first reported on the link between a “sweet spot” for Insulin Like Growth Factor I (IGF-I) in my article “Should You Use This Controversial Hormone Marketed As A Natural “Fountain Of Youth?”⁴³, and as the good folks at WellnessFX report in their article “The IGF-1 Trade-Off: Performance vs. Longevity”⁴⁴…

…”during the relatively recent fireside talk put together by WellnessFX, Tim Ferriss brought up the point that in some cases there may exist a trade-off or a “faustian bargain” (as he called it) between longevity and performance. Watch the fireside talk here. Optimizing for IGF-1, otherwise known as insulin-like growth factor-1, is one such case where more performance driven goals like maximizing growth and maintaining muscle and neurons may, to some degree, come at odds with ones desire for longevity.

The reason for this is that, aside from IGF-1’s more notorious role in building muscle, it has been shown to have some very interesting properties that haven’t entered mainstream dialogue as of yet: mice deprived of IGF-1 live longer…finding safe and effective ways to increase growth hormone and IGF-1 naturally, thereby, improving muscle and brain function while simultaneously preventing their atrophy seems like a no-brainer, who doesn’t want to be more fit and smarter – for longer?

Or is it longer? Mice, worms, and flies that are genetically engineered to be deficient in either growth hormone or IGF-1 live almost 50% longer than controls, which is a huge increase in lifespan. The converse has also shown to be also true: Overexpressing growth hormone by 100 to 1,000-fold in mice causes a 50% shorter lifespan, mainly due to kidney and liver dysfunction. The same results have been demonstrated in lower invertebrate species such as worms and flies, suggesting that this mechanism is evolutionarily conserved. Okay, admission here: either eliminating growth hormone or blasting it 1000-fold in mice is rather extreme…

…if you’re not quite convinced that the aging component to all of this is something that might also be relevant to humans consider this: polymorphisms (variations) in the gene that encodes for the IGF-1 receptor, which leads to decreased IGF-1 levels, have been associated with the longer lifespan found in centenarians.”

Ultimately, while the anecdote above sums things up pretty thoroughly, recommended levels of IGF can vary widely – but in a very eye-opening hormone replacement therapy podcast interview I recently conducted with anti-aging physician Dr. Richard Gaines⁴⁵, he recommended IGF-1 values between approximately 80 and 150 ng/ml.

9. Insulin

Low fasting insulin can be a crucial market for longevity, and indicates an important variable called “glycemic variability”, which is basically how often your blood sugar levels fluctuate throughout the day. My friends over at NourishBalanceThrive recently recorded an excellent episode with Dr. Bryan Walsh⁴⁶ about the extreme importance of glucose regulation and glycemic variability when it comes to longevity – and insulin is intimately tied to these variables.

For example, high fasting insulin levels are associated with a greater risk of cancer mortality. In addition, cancer patients who eat the highest amount of insulin-producing foods experience worsened cancer and increased overall mortality⁴⁸. Furthermore, high insulin levels can predict cancer mortality⁴⁹, even when controlling for confounding variables such as diabetes, obesity, and metabolic syndrome. In older adults with type 2 diabetes, the level of insulin use also predicts mortality⁵⁰.

The trick is not to eliminate insulin altogether, but to keep insulin levels within control. My friend Dr. Joseph Mercola recommends “a normal fasting blood insulin level…below 5, but ideally… below 3”.

10. Complete Blood Count w/ Differential

A complete blood count with differential, also known as a CBC, is often used as a broad screening test to determine an individual’s general health status. It can be used to screen for a wide range of conditions and diseases and to help diagnose various conditions, such as anemia, infection, inflammation, bleeding disorder or leukemia. The CBC is a panel of tests that evaluates the three types of cells that circulate in the blood, including:

Evaluation of white blood cells, the cells that are part of the body’s defense system against infections and cancer and also play a role in allergies and inflammation. White blood cell (WBC) count is a count of the total number of white blood cells in a person’s sample of blood, and identifies and counts the number of the various types of white blood cells present (the five types include neutrophils, lymphocytes, monocytes, eosinophils, and basophils).

Evaluation of red blood cells, the cells that transport oxygen throughout the body. Red blood cell (RBC) count is a count of the actual number of red blood cells in a person’s sample of blood. Other factors in this part of the panel include hemoglobin, MCV, MCH, MCHC, RDW, MPV and PDW. Hemoglobin measures the total amount of the oxygen-carrying protein in the blood, which generally reflects the number of red blood cells in the blood. Hematocrit measures the percentage of a person’s total blood volume that consists of red blood cells. Mean corpuscular volume (MCV) is a measurement of the average size of a single red blood cell. Mean corpuscular hemoglobin (MCH) is a calculation of the average amount of hemoglobin inside a single red blood cell. Mean corpuscular hemoglobin concentration (MCHC) is a calculation of the average concentration of hemoglobin inside a single red blood cell. Red cell distribution width (RDW) is a calculation of the variation in the size of RBCs. The mean platelet volume (MPV) may be reported with a CBC. It is a calculation of the average size of platelets. Platelet distribution width (PDW) is also be reported with a CBC, and reflects how uniform platelets are in size.

In the article “Which observations from the complete blood cell count predict mortality for hospitalized patients?”⁵², it is reported that he most impressive predictors of mortality to be derived from a CBC are burr cells, nucleated red blood cells (NRBCs), and absolute lymphocytosis (an increase in the number of lymphocytes in the blood.). In the analysis, the first two (burr and NRBC’s) were associated with mortality rates 8 to 10 times higher than that of the average admitted patient. There are anecdotal reports in the literature of burr cells being associated with “ominous prognosis” and more robust statistical analyses showing NRBCs to be associated with increased mortality. Lymphocytosis has also been reported as a mortality risk in patients, especially those with trauma and emergency medical conditions. The analysis shows that all 3 of these findings are strong independent predictors of mortality.

In addition, this article⁵³ reports that men and women with above-normal white blood cell counts could face an increased risk of death at an earlier age, particularly from cardiovascular disease. People with normal white cell counts may not be out of danger, since individuals on the high end of the normal range are also at increased risk of illness and death. Basically, the risk of cardiovascular mortality increases progressively with increasing white blood cell counts, and the increased risk of mortality associated with high white blood cell (counts) is maintained over 40 years of follow-up! You can read a host of other studies on RBC and WBC’s association with mortality here⁵⁴.

Summary

So there you have it: pay attention to qualitative, objective variables such as love, life, relationships, healthy food, fasting, grip strength and more – but also use modern science to track important internal variables and the biomarkers you’ve just discovered in this new Anti-Aging panel. The only test not included here, but that I still highly recommend, is the “Teloyears” telomere test. You can learn more about that test here⁵⁵.

Finally, you may be curious how this test is different than the more expensive and more comprehensive Longevity panel that I designed in conjunction with WellnessFX⁵⁶. The simple answer is that for this anti-aging biomarkers test, I’ve chosen the best of the best and reduced the cost so that it is repeatable and fast for you. The Longevity panel is certainly a good, very comprehensive test, but something you would do, for example, just once or twice per year, whereas you can repeat this Anti-Aging panel as often as once a month to once a quarter, and get very fast and easy-to-interpret results.

Upon ordering this test, you will be given a simple .pdf that you can download, print and bring to any lab near your home for a quick and easy blood draw. Within a week, you’ll have the results in your hands, and be given access to a trained medical professional or consultant such as myself to review your results with you!

Order your Greenfield Anti-Aging Biomarkers Lab test >>

Want More on Anti-Aging?

Here are a few of my other popular posts and podcasts on the topic:

About Ben Greenfield

Ben Greenfield is an ex-bodybuilder, Ironman triathlete, Spartan racer, coach, speaker and author of the New York Times Bestseller “Beyond Training: Mastering Endurance, Health and Life.” In 2008, Ben was voted as NSCA’s Personal Trainer of the year and in 2013 and 2014 was named by Greatist as one of the top 100 Most Influential People In Health And Fitness. Ben blogs and podcasts at http://www.BenGreenfieldFitness.com, and resides in Spokane, WA with his wife and twin boys.

Courtesy of Ben Greenfield

References

https://en.wikipedia.org/wiki/Blue_Zone
https://greenfieldfitnesssystems.com/product/greenfield-anti-aging-biomarkers-lab-testing/
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0058278
https://www.ncbi.nlm.nih.gov/pubmed/27261330/
C van-A van-M Abdelrazek-P Weijs-M Tieland https://www.ncbi.nlm.nih.gov/pubmed/28711425
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636678/
https://www.ncbi.nlm.nih.gov/pubmed/7768242
https://www.ncbi.nlm.nih.gov/pubmed/8382141
https://www.ncbi.nlm.nih.gov/pubmed/12618573
https://www.ncbi.nlm.nih.gov/pubmed/14964443
https://www.ncbi.nlm.nih.gov/pubmed/11706288
https://www.ncbi.nlm.nih.gov/pubmed/20020786
https://www.ncbi.nlm.nih.gov/pubmed/15944465
https://www.ncbi.nlm.nih.gov/pubmed/20020786
https://www.ncbi.nlm.nih.gov/pubmed/17090425
https://www.ncbi.nlm.nih.gov/pubmed/18522489
https://www.ncbi.nlm.nih.gov/pubmed/19751412
https://www.ncbi.nlm.nih.gov/pubmed/17693256
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636678/
https://www.webmd.com/women/guide/normal-testosterone-and-estrogen-levels-in-women
https://www.ncbi.nlm.nih.gov/pubmed/16631506
https://www.ncbi.nlm.nih.gov/pubmed/14504253
http://blog.wellnessfx.com/2012/09/27/biomarker-series-high-sensitivity-c-reactive-protein-a-beacon-for-inflammation/
https://www.ncbi.nlm.nih.gov/pubmed/16526201
https://www.ncbi.nlm.nih.gov/pubmed/28254109
https://www.ncbi.nlm.nih.gov/pubmed/28913629
https://www.google.com/search?q=triglyceride%3AHdl+ratio+mortality&oq=triglyceride%3AHdl+ratio+mortality&aqs=chrome..69i57j69i58.8094j0j4&sourceid=chrome&ie=UTF-8
https://www.ncbi.nlm.nih.gov/pubmed/24402298
https://www.wellnessfx.com/advanced-heart-health
https://www.drsinatra.com/why-your-cholesterol-test-can-lie
https://www.ncbi.nlm.nih.gov/pubmed/24616707
https://www.ncbi.nlm.nih.gov/pubmed/28660850
https://www.ncbi.nlm.nih.gov/pubmed/28831714
https://www.ncbi.nlm.nih.gov/pubmed/22371413
https://lipidworld.biomedcentral.com/articles/10.1186/s12944-017-0552-0
https://www.researchgate.net/publication/20817833_Erythrocyte_Stearic_to_Oleic_Acid_Ratio_in_Prostatic_Carcinoma
https://www.ncbi.nlm.nih.gov/pubmed/2242696
https://www.ncbi.nlm.nih.gov/pubmed/12793905
http://www.ncbi.nlm.nih.gov/pubmed/16908801
http://jcem.endojournals.org/cgi/content/full/93/1/68http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190742/
http://abcnews.go.com/Health/ActiveAging/story?id=3247773&page=1&page=1
http://jeffreydachmd.com/2016/12/low-testosterone-associated-with-increased-mortality/
https://bengreenfieldfitness.com/article/hormones-articles/is-igf-1-healthy/
http://blog.wellnessfx.com/2013/09/04/igf-1-trade-performance-vs-longevity/
https://bengreenfieldfitness.com/podcast/how-testosterone-injections-work/
http://www.nourishbalancethrive.com/podcasts/nourish-balance-thrive/how-understand-glucose-regulation/
https://www.ncbi.nlm.nih.gov/pubmed/28390156
https://www.ncbi.nlm.nih.gov/pubmed/28817837
https://www.ncbi.nlm.nih.gov/pubmed/22215126
https://www.ncbi.nlm.nih.gov/pubmed/28314486
https://fitness.mercola.com/sites/fitness/archive/2012/04/27/vitamin-d-and-blood-test-health-factors.aspx
https://www.medscape.com/viewarticle/553947_4
https://www.medicinenet.com/script/main/art.asp?articlekey=80924
https://www.google.com/search?q=white+blood+cell+red+blood+cell+count+mortality&oq=white+blood+cell+red+blood+cell+count+mortality&aqs=chrome..69i57.5464j0j4&sourceid=chrome&ie=UTF-8
https://bengreenfieldfitness.com/podcast/self-quantification-podcasts/how-to-test-your-telomere-length/
https://greenfieldfitnesssystems.com/?s=longevity&post_type=product

The posts on this blog are for information only, and are not intended to substitute for a doctor-patient or other healthcare professional-patient relationship nor do they constitute medical or healthcare advice of any kind. Any information in these posts should not be acted upon without consideration of primary source material and professional input from one's own healthcare professionals.

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