Life Extension Magazine®
Aging results in a progressive decline in functions of living systems.1 Factors that influence aging include cell senescence, poor nutrition, and stem cell exhaustion.
A measurable aspect of normal aging is DNA methylation, a process that can favorably or unfavorably regulate gene expression.2-4
DNA methylation is so closely connected to age-related changes that one review article called it "the 'prophet' of age-related outcomes."5
A compound called SAMe (S-Adenosyl-Methionine) is a cofactor involved in DNA methylation that helps regulate healthy gene expression.6
By doing so, SAMe can help combat some common causes of age-related decline and could even play a role in prolonging life.5,7Understanding DNA Methylation
Genes are made up of DNA.
Our bodies turn genes "on" or "off" as necessary. One of the switches that modulates the way genes are expressed is a process called methylation.
Methylation happens when methyl groups are added to the DNA without changing the DNA sequence. Methylation is essential for healthy cellular functions.8
The science of epigenetics studies how and why and whether genes are expressed or not. One of the key types of epigenetic modification is DNA methylation. DNA methylation is a key switch that usually silences the expression of a gene or "turns it off."9
This occurs when methyl groups are attached to the DNA.10
The compound SAMe is found naturally in the body. Although it is required for many biochemical reactions,11 one of the most important processes SAMe is involved in is methylation.6,7 SAMe is the body's primary methyl donor.10,12
If we don't have enough of it, the body cannot methylate properly. That can lead to excessive inflammation, tissue damage, and organ failures.13 Healthy methylation patterns can help degenerative disorders and slow certain aging processes.
Alzheimer’s Disease
Disturbances in DNA methylation have been identified as one of the potential drivers of Alzheimer's disease.14,15
Research has shown that Alzheimer's patients have very low levels of SAMe.16,17
In an animal Alzheimer's model study, SAMe improved cognitive impairment in four weeks, by upregulating early overall DNA demethylation to reduce amyloid pathology.1
In four patients with Alzheimer's, 1,200 mg of SAMe daily, in a divided dose for four to eight months increased the level of SAMe in cerebrospinal fluid by 62.5%.16
Osteoarthritis
Improper methylation impacts two hallmarks of osteoarthritis: inflammation18,19 and cartilage damage.20,21
By getting methylation back on track, SAMe may modulate those genes and suppress inflammation.22
In a meta-analysis, scientists found that SAMe was as effective as NSAID (non-steroidal anti-inflammatory drugs) in alleviating pain and optimizing joint function.23
In 2 clinical trials, participants with osteoarthritis of the knee were randomized to receive NSAID or SAMe (1200 mg) per day in divided doses. Participants were evaluated after 8- 16 weeks, it was found that SAMe was as effective as NSAID in management of symptoms of knee osteoarthritis.24,25 There were no significant differences in pain relief or tolerability between NSAID or SAMe group.24
Remarkably, SAMe was shown in one study to stimulate production of new cartilage in animals.26 This can potentially be beneficial to slowing or reversing the progress of osteoarthritis.
Prolonging Life
Studies show that aging itself is associated with alterations in DNA methylation.2,3,27 Methylation isn't just linked to the development of age-related diseases; it also has direct impact on lifespan itself.27,28
In one study, giving SAMe to tumor-prone mice prevented the development of liver tumors. It did this by restoring methylation and turning on tumor-suppressor genes.29
A study of yeast showed that stimulating SAMe synthesis extended lifespan by activating a well-known enzyme called AMPK (AMP-activated protein kinase).30 AMPK has been referred to as a "metabolic master switch." In humans APMK helps the body utilize calories more efficiently, reduces fat accumulation, and enhances cleaning of cellular junk.31
Summary
The way genes are expressed has a great impact on our health and longevity.
DNA methylation is a process that regulates gene expression.
SAMe (S-Adenosyl-Methionine) is an essential factor involved in DNA methylation.
Defects in methylation can lead to chronic disorders.
Increasing SAMe intake provides the body with a critical methylation nutrient, which can help modulate the way genes are expressed.
SAMe has shown clinical success in cases of osteoarthritis. Early studies suggest SAMe's status as the body's preferred methylation nutrient. It may help contribute to longer lifespans.
If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.
References
- Zhang Y, Ma R, Deng Q, et al. S-adenosylmethionine improves cognitive impairment in D-galactose-induced brain aging by inhibiting oxidative stress and neuroinflammation. J Chem Neuroanat.2023 Mar;128:102232.
- Salameh Y, Bejaoui Y, El Hajj N. DNA Methylation Biomarkers in Aging and Age-Related Diseases. Front Genet.2020;11:171.
- Bell CG, Lowe R, Adams PD, et al. DNA methylation aging clocks: challenges and recommendations. Genome Biol.2019 Nov 25;20(1):249.
- Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY).2019 Jan 21;11(2):303-27.
- Xiao FH, Wang HT, Kong QP. Dynamic DNA Methylation During Aging: A "Prophet" of Age-Related Outcomes. Front Genet.2019 2019-February-18;10(107):107.
- Gao J, Cahill CM, Huang X, et al. S-Adenosyl Methionine and Transmethylation Pathways in Neuropsychiatric Diseases Throughout Life. Neurotherapeutics.2018 Jan;15(1):156-75.
- Loenen WAM. S-Adenosylmethionine Metabolism and Aging. In: Moskalev A, Vaiserman AM, editors. Epigenetics of Aging and Longevity. Vol 4. Boston: Academic Press; 2018:59-93.
- Loscalzo J, Handy DE. Epigenetic modifications: basic mechanisms and role in cardiovascular disease (2013 Grover Conference series). Pulm Circ. 2014 Jun;4(2):169-74.
- Mahmoud AM, Ali MM. Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome. Nutrients.2019 Mar 13;11(3):608.
- Glier MB, Green TJ, Devlin AM. Methyl nutrients, DNA methylation, and cardiovascular disease. Mol Nutr Food Res.2014 Jan;58(1):172-82.
- Available at: https://www.nccih.nih.gov/health/sadenosyllmethionine-same-in-depth . Accessed April, 26, 2023.
- Laurino P, Tawfik DS. Spontaneous Emergence of S-Adenosylmethionine and the Evolution of Methylation. Angew Chem Int Ed Engl. 2017 Jan 2;56(1):343-5.
- Rotondo JC, Selvatici R, Di Domenico M, et al. Methylation loss at H19 imprinted gene correlates with methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males. Epigenetics. 2013 Sep;8(9):990-7.
- Wei X, Zhang L, Zeng Y. DNA methylation in Alzheimer's disease: In brain and peripheral blood. Mech Ageing Dev.2020 Oct;191:111319.
- Huo Z, Zhu Y, Yu L, et al. DNA methylation variability in Alzheimer's disease. Neurobiol Aging.2019 Apr;76:35-44.
- Bottiglieri T, Godfrey P, Flynn T, et al. Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry. 1990 Dec;53(12):1096-8.
- Linnebank M, Popp J, Smulders Y, et al. S-Adenosylmethionine Is Decreased in the Cerebrospinal Fluid of Patients with Alzheimer’s Disease. Neurodegenerative Diseases.2010;7(6):373-8.
- Shen J, Abu-Amer Y, O'Keefe RJ, et al. Inflammation and epigenetic regulation in osteoarthritis. Connect Tissue Res.2017 Jan;58(1):49-63.
- Reynard LN. Analysis of genetics and DNA methylation in osteoarthritis: What have we learnt about the disease? Semin Cell Dev Biol. 2017 Feb;62:57-66.
- Monteagudo S, Cornelis FMF, Aznar-Lopez C, et al. DOT1L safeguards cartilage homeostasis and protects against osteoarthritis. Nat Commun. 2017 Jun 19;8:15889.
- Jeffries MA, Donica M, Baker LW, et al. Genome-Wide DNA Methylation Study Identifies Significant Epigenomic Changes in Osteoarthritic Subchondral Bone and Similarity to Overlying Cartilage. Arthritis Rheumatol. 2016 Jun;68(6):1403-14.
- Miranda-Duarte A. DNA Methylation in Osteoarthritis: Current Status and Therapeutic Implications. Open Rheumatol J.2018;12:37-49.
- Soeken KL, Lee WL, Bausell RB, et al. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract.2002 May;51(5):425-30.
- Kim J, Lee EY, Koh EM, et al. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients. Clin Ther.2009 Dec;31(12):2860-72.
- Najm WI, Reinsch S, Hoehler F, et al. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495]. BMC Musculoskelet Disord. 2004 Feb 26;5:6.
- Hosea Blewett HJ. Exploring the mechanisms behind S-adenosylmethionine (SAMe) in the treatment of osteoarthritis. Crit Rev Food Sci Nutr. 2008 May;48(5):458-63.
- Xiao FH, Kong QP, Perry B, et al. Progress on the role of DNA methylation in aging and longevity. Brief Funct Genomics.2016 Nov;15(6):454-9.
- McEwen LM, Morin AM, Edgar RD, et al. Differential DNA methylation and lymphocyte proportions in a Costa Rican high longevity region. Epigenetics Chromatin. 2017;10:21.
- Stoyanov E, Mizrahi L, Olam D, et al. Tumor-suppressive effect of S-adenosylmethionine supplementation in a murine model of inflammation-mediated hepatocarcinogenesis is dependent on treatment longevity. Oncotarget.2017 Dec 1;8(62):104772-84.
- Ogawa T, Tsubakiyama R, Kanai M, et al. Stimulating S-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK. Proc Natl Acad Sci U S A.2016 Oct 18;113(42):11913-8.
- Ouyang Y, Wu Q, Li J, et al. S-adenosylmethionine: A metabolite critical to the regulation of autophagy. Cell Prolif.2020 Nov;53(11):e12891.