Study Reverses Biological Age by 2.5 Years with HGH, DHEA and Metformin Cocktail

It may be possible to turn back the aging process with a prescription drug formula

A scientific trial combining three drugs surprised researchers when it surpassed its original goal of slowing age-related deterioration of the immune system. The drug cocktail of Human Growth Hormone, DHEA and metformin, also made the nine male participants 2.5 years younger.

The achievement is hailed as the first human trial to reverse age. The success was measured using four different methods to analyze genomic markers that identify epigenetic age (biological age).

 Biological markers used in the study

  • Horvath epigenetic age which identifies chronological and genomic age by analyzing DNA changes (methylation) in human tissues and cell types.1
  • GrimAge criteria which uses genomic analysis to strongly predict lifespan and health span.2
  • Hannum epigenetic aging which measures DNA methylation across the course of human life to compare the age of a cancerous tissue with that of non-cancerous tissue and other biomarkers in the same person. It is also highly accurate predicting the outcome of age-related illnesses and life span.3
  • PhenoAge which uses several biological markers to analyze diseases such as cancer and Alzheimer's as well as physical functioning to predict lifespan and healthspan.4

The study was first published in the scientific journal Aging Cell and then later reported in the journal Nature. UCLA geneticist Steve Horvath analyzed genomic markers from blood samples collected in the study.

Although the trial was small and further research is necessary to determine efficacy and safety, it shows promise to treat age-related diseases. Horvath called the study's results unexpected and "futuristic."

Why did the study mix HGH, Metformin and DHEA?

To clarify, the study used recombinant human growth hormone, which technically is abbreviated as rhGH or rHGH and called somatropin. Outside of scientific and medical fields, when people speak of rhGH they commonly refer to it as HGH.

Somatropin is manufactured and close to identical to natural Growth Hormone (GH) created by the body. The study focused on rhGH's potential to regenerate the thymus and immune system as demonstrated in animal studies. However, rhGH poses several health risks. In fact, HGH is illegal in the US for anything other than its FDA-approved use,

One of the dangers of rHGH is insulin resistance, which can lead to Type II Diabetes. Metformin and DHEA were added to reduce this risk.

Metformin and DHEA to lower blood glucose

Metformin is FDA-approved to treat Type II diabetes by helping the body maximize the use of its own natural insulin supply, limiting intestinal absorption of sugar and reducing the liver's production of sugar. Although it is not FDA-approved to counteract insulin resistance, studies show DHEA has those benefits.DHEA is a hormone that is a precursor to androgens and can increase testosterone. 

Why is HGH popular for antiaging?

Its illicit status has not hurt HGH's popularity as an off-label injectable antiaging elixir. Despite its steep price (thousands of dollars a month) HGH has been used for years by celebrities who swear by its effects. A-Listers like A. Rod, Suzanne Somers and Sylvester Stallone have cited increased muscle mass and decreased fat, improved muscle recovery, weight loss, skin regeneration, better sleep and younger-looking skin. Clinical trials have also shown similar results,6 but the FDA has ruled that HGH causes more risks than benefits when used as an off-label drug.

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What is off label-drug use?

Prescribing a drug for uses other than its FDA-approved indications is called "off-label. It is legal, and one in five prescriptions is written "off-label." An example of off-label drug use is metformin for anti-aging.

Growing researching suggests that metformin may help improve cognitive brain function in patients with mild cognitive impairment as well as abnormal glucose metabolism. The effect may be related to its ability to improve the body's use of insulin. This prevents the overproduction of glycogen (a precursor to glucose) by the liver. Metformin also reportedly crosses the blood-brain barrier and helps decrease inflammation. Absent of inflammation, the brain is able to metabolize energy efficiently. The brain uses high levels of energy to function. Much of it is glucose dependent.7

Metformin to improve cognitive function - off-label use

Study’s success rebuilding immunity

The positive impact on the immune system was more than expected. Not only did the thymus regenerate but bone marrow did as well. This led to the most quantifiable result: increased ratio of protective white blood cells (lymphocytes) to monocyte white blood cells, abbreviated as LMR.

Although monocytes are important to the immune system, chronically high levels cause/are signs of inflammation and autoimmune diseases, among other health conditions. LMR blood levels can provide insight on prognosis for cancer patients, liver cirrhosis, the progression of systemic inflammation and a host of life-threatening diseases.8

The original trial called the TRIIM (Thymus Regeneration, Immunorestoration, and Insulin Mitigation) began in 2015 and concluded in 2017. Gregory Fahy, the chief scientific officer and co-founder of Intervene Immune in Los Angeles, led the trial. The TRIIM trial investigated the use of synthetic HGH to regenerate the thymus in men 51‐65‐years‐old.

That age range is the point right before thymus activity is substantially reduced or stops completely. Although T-cells are produced in bone marrow, all of their activity is conducted in the thymus. The majority of T-cells die in the thymus even in younger populations. With a compromised thymus later in life, T-cell population naturally plummets. 

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Why does the thymus shrink as we age?

During the aging process the thymus deteriorates to fatty tissue. In some elderly adults, the thymus becomes incapable of supporting healthy white blood cells, known as T-Cells. With decreased T-Cells, diseases, illnesses and eventual death gain ground. Researchers think they have identified a cell that may play a role in the transformation of the thymus into fatty tissue.10 Additionally, production of T-Cell production slows naturally with age.

For more news about drugs used for anti-aging and health benefits read: Vitamin B12 Deficiency: Causes and How to Prevent and Treat It. Discover skincare anti-aging products and custom-made prescriptions designed to enhance female and male sexual satisfaction. 

References

1 Horvath, Steve. DNA methylation age of human tissues and cell types. Genome Biology. Volume 14, Article number: 3156 (2013). https://genomebiology.biomedcentral.com/articles/10.1186/gb-2013-14-10-r115

2 Ake T. Lu. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging. 2019 Jan 21;11(2):303-327. doi: 10.18632/aging.101684

3 Hannum, Gregory. Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Molecular Cell. 2013 Jan 24; 49 (2): 359-367. doi.org/10.1016/j.molcel.2012.10.016

Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573–591. doi:10.18632/aging.101414

5 Weiss EP, Villareal DT, Fontana L, Han DH, Holloszy JO. Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans. Aging (Albany NY). 2011;3(5):533–542. doi:10.18632/aging.100327 

6 Tavares AB, Micmacher E, Biesek S, et al. Effects of Growth Hormone Administration on Muscle Strength in Men over 50 Years Old. Int J Endocrinol. 2013;2013:942030. doi:10.1155/2013/942030

Lin Y, Wang K, Ma C, et al. Evaluation of Metformin on Cognitive Improvement in Patients With Non-dementia Vascular Cognitive Impairment and Abnormal Glucose Metabolism [published correction appears in Front Aging Neurosci. 2018 Oct 12;10:322]. Front Aging Neurosci. 2018;10:227. Published 2018 Jul 27. doi:10.3389/fnagi.2018.00227

8 Lee JS, Kim NY, Na SH, Youn YH, Shin CS. Reference values of neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South Korea. Medicine (Baltimore). 2018;97(26):e11138. doi:10.1097/MD.000000000001113

9 Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Generation of lymphocytes in bone marrow and thymus. Available from: https://www.ncbi.nlm.nih.gov/books/NBK27123/

10 Sheridan, Julie M. Thymospheres Are Formed by Mesenchymal Cells with the Potential to Generate Adipocytes, but Not Epithelial Cells. Cel Reports. 2017 Oct 24 21(4)934-942. doi.org/10.1016/j.celrep.2017.09.090

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