I’m not a big believer in magic bullets. Everything he’s ever learned says that you’re only as strong as your weakest link. That’s why he’s always preached that the key to health is raising your entire Baseline of Health. But that said, he admits that what we’re talking about here today is a uniquely important anti-aging discovery.

The best place to start is at the beginning by addressing the question: what is aging? What makes us age? In fact, there are many factors that contribute to old age. Some, like joint degradation, happen at the macro level. Some, like free radical damage, happen at the micro level. And then, of course, there are hormonal changes. But of all the things that make us “old,” two stand out because, until recently, they have been so untouchable:

• The Hayflick Limit
• The glycation of proteins

The Hayflick Limit: Cell Lifespan and L. Carnosine

The Hayflick Limit is named after the person who discovered it almost 40 years ago. A quick description is that all cells have only a limited capacity to continue to divide through the course of our lives.¹ “Hayflick Limit.” ScienceDirect. (Accessed 31 May 2018.) http://www.sciencedirect.com/topics/medicine-and-dentistry/hayflick-limit

Those numbers are different for each type of cell in our body, and by early adulthood, half of those divisions have been used up. By mid-life, maybe only 20-39% of those divisions are left. At that point, old age starts taking over — then death.

This limited capacity of a cell to perpetuate itself is called the Hayflick Limit. In effect, the Hayflick Limit determines life span at the cellular level. With each division, a cell becomes less likely to divide again, until finally it stops dividing altogether and becomes what we call senescent.

Cell senescence is the final step before cell death. Senescent cells are still alive and metabolically active, but they’re no longer capable of dividing. More importantly, though, senescent cells exhibit all the characteristics that so bother us about old age, such as the difference between the supple skin of a child and the wrinkled skin of the elderly.

How do cells age?

As cells approach the Hayflick Limit, they divide less frequently and become aberrant. They take on wildly irregular forms. They no longer line up in parallel arrays; they assume a granular appearance and deviate from their normal size and shape. This distorted appearance, called the senescent phenotype, is accompanied by a state of declining functionality that, until recently, was thought to be irreversible.

As it turns out, not only can we now reverse the aging process at the cellular level and do it quite simply and quickly — but we can also reverse aging at the system level and the organ level. And for that matter, we can reverse it in terms of how we look and feel — and by that we mean our skin and hair and energy levels. And then, of course, we can even reverse aging in terms of lifespan.

What’s the Secret?

The nutraceutical I’m talking about is L-carnosine. It’s a naturally occurring combination of two amino acids, alanine and histidine, that was discovered in Russia in the early 1900s. Because much of the early research was done in Russia, it was largely unavailable in the United States for decades. Now, though, there have been many studies and experiments in other parts of the world verifying everything done in Russia — and more.

Most notably, there were a series of astonishing experiments done in Australia that proved that carnosine rejuvenates cells as they approach senescence. Cells cultured with carnosine lived longer and retained their youthful appearance and growth patterns.² McFarland GA, Holliday R. “Retardation of the senescence of cultured human diploid fibroblasts by carnosine.” Exp Cell Res. 1994 Jun;212(2):167-75. http://www.ncbi.nlm.nih.gov/pubmed/8187813 , ³ McFarland GA, Holliday R. “Further evidence for the rejuvenating effects of the dipeptide L-carnosine on cultured human diploid fibroblasts.” Exp Gerontol. 1999 Jan;34(1):35-45. http://www.ncbi.nlm.nih.gov/pubmed/10197726

What’s probably the most exciting result of the studies is that it was discovered that carnosine can reverse the signs of aging in senescent cells.

The Reversal of Aging

When the scientists transferred senescent cells to a culture medium containing carnosine, those cells exhibited a rejuvenated appearance and often an enhanced capacity to divide. When they transferred the cells back to a medium lacking carnosine, the signs of senescence quickly reappeared.

As they switched the cells back and forth several times between the culture media, they consistently observed that the carnosine medium restored the juvenile cell phenotype within days, whereas the standard culture medium brought back the senescent cell phenotype.⁴ McFarland. Retardation.

Increase Cell Life

In addition, the carnosine medium increased cell life span — even for old cells. When the researchers took old cells that had already gone through 55 divisions and transferred them to the carnosine medium, they survived up to 70 divisions, compared to only 57 to 61 divisions for the cells that were not transferred.

This represents an increase in the number of cell divisions for each cell of almost 25%.

But in terms of cell life, the increase was an astounding 300%. The cells transferred to the carnosine medium attained a life span of 413 days, compared to just 126 to 139 days for the control cells.

Increase Life Expectancy

This is mind-boggling. But so far, all we’ve talked about are cells. What does carnosine mean for actual life expectancy?

A more recent Russian study has shown that mice given carnosine are twice as likely to reach their maximum lifespan as untreated mice.⁵ Gallant S, Semyonova M, Yuneva M. “Carnosine as a potential anti-senescence drug.” Biochemistry (Mosc). 2000 Jul;65(7):866-8. http://protein.bio.msu.ru/biokhimiya/contents/v65/full/65071018.html The carnosine also significantly reduced the outward “signs of old age.”⁶ Boldyrev AA, Gallant SC, Sukhich GT. “Carnosine, the protective, anti-aging peptide.” Biosci Rep. 1999 Dec;19(6):581-7. http://www.ncbi.nlm.nih.gov/pubmed/10841274

In effect, it made the mice look younger. 44% of the carnosine treated mice had young, glossy coats in old age as opposed to only 5% in the untreated mice. This represents 900% better odds of looking young in old age.

Feel Young Again

Another important difference between the treated and the untreated mice was in their behavior. Only 9% of the untreated mice behaved youthfully in old age, versus 58% of the carnosine treated mice. That’s a 600% improvement in how they felt.

Strong Antioxidant

Quite simply, carnosine is one of the most powerful antioxidants known. It’s a great heavy-metal scavenger. It’s a powerful auto-regulator. And it stands alone when it comes to preventing and reversing protein glycation or cross-linking (more on this in a moment).

Auto-Regulator

Carnosine has the remarkable ability to throttle down bodily processes that are in a state of excess, and to ramp up those that are under expressed.

For example, carnosine thins the blood of people whose blood tends to clot too much and increases the clotting tendency in those with a low clotting index.

Another example is that carnosine suppresses excess immune responses (specifically, neutrophil function) in those who have “hyper” immune systems, whereas it stimulates the response in those with weakened immune systems — such as the aged.⁷ Tan, K.M., Candlish, J.K. “Carnosine and anserine as modulators of neutrophil function.” Clin. Lab. Haematol. 1998 Aug; 20(4): 239-44. http://www.researchgate.net/publication/13509482_Carnosine_and_anserine_as_modulators_of_neutrophil_function

And carnosine even seems to have the ability to normalize brain wave functions.

Protein Glycation: Sugar and Aging

Glycation is the uncontrolled reaction of sugars with proteins. It’s kind of like what happens to sugars when you heat them and they caramelize. In effect, glycation is what happens when excess sugars caramelize the proteins in your body. It’s a major factor in the aging process — and it’s particularly devastating to diabetics.

Your body is mostly made up of proteins. In fact, proteins are the substances most responsible for the daily functioning of your body. That’s why anything that causes protein deterioration has such a dramatic impact on the body’s function and appearance.

Thanks largely to the destructive effect of sugar and aldehydes, the protein in our bodies tends to undergo destructive changes as we age. This destruction is a prime factor, not only in the aging process itself, but also in the familiar signs of aging such as wrinkling skin, cataracts, and the destruction of our nervous system — particularly our brains. Studies show that carnosine is effective against all these forms of protein modification.⁸ Hipkiss AR. “Carnosine, a protective, anti-ageing peptide?” Int J Biochem Cell Biol. 1998 Aug;30(8):863-8. http://www.ncbi.nlm.nih.gov/pubmed/9744078

Protein Modification for Longevity

As previously stated, aging is associated with damage to cellular proteins. But carnosine protects cellular proteins from damage in at least two ways.

• First, it bonds with the carbonyl (or aldehyde) groups that if left alone will attack and bind with proteins.

2. Second, it works as an antioxidant to prevent the formation of oxidized sugars, also called Advanced Glycosylation End-products or AGEs for short.⁹ “Advanced glycation end-product.” ScienceDirect. (Accessed 1 Jun 2018.) http://www.sciencedirect.com/topics/medicine-and-dentistry/advanced-glycation-end-product That’s really the caramelization thing that we mentioned earlier. In more technical terms, the mechanism by which AGEs induce damage is through a process called cross-linking that causes intracellular damage and cell death.¹⁰ Shaikh S, Nicholson LF. “Advanced glycation end products induce in vitro cross-linking of alpha-synuclein and accelerate the process of intracellular inclusion body formation.” J Neurosci Res. 2008 Jul;86(9):2071-82. http://www.ncbi.nlm.nih.gov/pubmed/18335520 The bottom line here is that the less AGEs, in your body, the younger you are.

Both these processes have important implications for anti-aging therapy. The key is that carnosine not only prevents damaging cross-links from forming, it eliminates cross-links that have previously formed in proteins, thus restoring normal membrane function.¹¹ Hipkiss AR, Michaelis J, Syrris P. “Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross-linking agent.” FEBS Lett. 1995 Aug 28;371(1):81-5. http://febs.onlinelibrary.wiley.com/doi/epdf/10.1016/0014-5793%2895%2900849-5

Alzheimer’s

Carnosine has been proven to reduce or completely prevent cell damage caused by beta amyloid, one of the prime protein risk factors for Alzheimer’s. The presence of beta amyloid leads to damage of the nerves and arteries of the brain. Carnosine blocks and inactivates beta amyloid. In effect, it protects neural tissues against dementia.  The key, as we’ve already seen, is that carnosine not only prevents damaging cross-links from forming in proteins, it eliminates cross-links that have previously formed in those proteins, thus restoring normal membrane function in cells. This is true not only in the brain, but in all the organs of our body — our skin included. Keep in mind that the damage you see in the skin is not just a cosmetic issue. That damage is absolutely an indicator of the kinds of damage happening to every other organ in your body — including your eyes and your brain.

The Reversal of Age

While it is true that many people who supplement with carnosine are going to notice everything from younger looking skin to more energy, the bottom line is that you really shouldn’t look for any short-term benefits from carnosine supplementation. If any short-term benefits are noticed, you should consider them a bonus. The reason you want to supplement with carnosine is for the long-term, not for the short-term benefits that you may or may not notice. You supplement with carnosine to protect against the long-term ravages of aging.

Carnosine levels in our body directly correlate with both the length and quality of our lives. And since carnosine levels decline with age, supplementation with carnosine represents one of the most powerful things you can do to hold back the ravages of old age.

Carnosine Studies 2013-2014

Most recent studies involving carnosine have no direct connection with anti-aging, which is difficult for researchers to quantify. Instead, now that carnosine is considered “real” by the scientific community, the studies tend to be much more specific–and quantifiable–with an emphasis on the role carnosine supplementation can play in reversing things like cardiovascular disease, cancer, and dementia. What makes these studies especially interesting is that although they involve measuring benefits in specific areas of the body, those benefits can easily be extrapolated to the body as a whole, thus serving as confirmation of carnosine’s overall anti-aging benefits. Here’s a sampling.

Carnosine Benefits and Your Cardiovascular System

As we just discussed, carnosine has been shown to modulate triglyceride and glycation levels in both cell and animal systems. But a 2014 study took things one step further when it concluded that long term supplementation with carnosine may, in fact, lower triglyceride levels and thus suppress plaque instability in diabetes-associated atherosclerosis.¹² Brown BE, Kim CH, Torpy FR, Bursill CA,et al. “Supplementation with carnosine decreases plasma triglycerides and modulates atherosclerotic plaque composition in diabetic apo E(-/-) mice.” Atherosclerosis. 2014 Feb;232(2):403-9. http://www.ncbi.nlm.nih.gov/pubmed/24468155

And there’s more.

Atherosclerotic lesions are also associated with the accumulation of reactive aldehydes formed from the oxidation of fats in the bloodstream. But carnosine helps here too. A study published in 2013 suggests that carnosine inhibits atherogenesis (the formation of arterial plaque) by facilitating aldehyde removal from atherosclerotic lesions.¹³ Barski OA, Xie Z, Baba SP, Sithu SD, et al. “Dietary carnosine prevents early atherosclerotic lesion formation in apolipoprotein E-null mice.” Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1162-70. http://www.ncbi.nlm.nih.gov/pubmed/23559625 This should not be a surprise as we just discussed that one of the primary benefits of carnosine is that it bonds with carbonyl (or aldehyde) groups that if left alone attack and bind with proteins–thus destroying them. According to this study, deep tissue levels of carnosine may be an important determinant of atherosclerotic lesion formation, and treatment with carnosine could be a useful therapy for the prevention–or the treatment of–atherosclerosis.

Carnosine Benefits and Cancer

Back in 2012, I reported on studies that showed that carnosine protects against genetic structure damage caused by the chemotherapy drug cyclophosphamide. This is significant because cyclophosphamide is one of the most widely used chemotherapy drugs in treating cancers. But there’s another problem with cyclophosphamide beyond its tendency to destroy DNA: it suppresses the ability of the body to create new blood cells. It makes you anemic. Well, more recent studies have found that carnosine has the potential to promote recovery from the blood building suppression induced by cyclophosphamide, as well as other chemotherapy agents, and that it can substantially improve the overall anti-tumor effects of the standard chemotherapies.¹⁴ Xu M1, He RR, Zhai YJ, Abe K, Kurihara H. “Effects of carnosine on cyclophosphamide-induced hematopoietic suppression in mice.” Am J Chin Med. 2014;42(1):131-42. http://www.ncbi.nlm.nih.gov/pubmed/24467540

So, why is this important to you–assuming you don’t have cancer at the moment?

Because cancer and old age are not dissimilar. They both involve the relentless diminishing of cellular DNA, cellular integrity, and ultimately cellular function. The fact that carnosine can protect against this tri-headed assault when your body is confronted by some of the most toxic drugs known attests to its ability to protect against the same kind of assault presented by simple aging.

Meanwhile, a 2014 study published in the journal Amino Acids looked at just how carnosine might inhibit the growth of tumor cells.¹⁵ Hipkiss AR1, Gaunitz F. “Inhibition of tumour cell growth by carnosine: some possible mechanisms.” Amino Acids. 2014 Feb;46(2):327-37. http://www.ncbi.nlm.nih.gov/pubmed/24292217 Possibilities include effects on:

• Glycolytic enzymes
• Metabolic regulatory activities
• Redox biology
• Protein glycation
• Glyoxalase activity
• Apoptosis
• Gene expression
• Metastasis

The authors stated that it is possible, by acting at various sites, that this “pluripotent dipeptide” [their exact words] might be an example of an internally produced “smart drug” [again, their exact words].

And finally, a study published in Andrologia found that carnosine can protect against both the damage and dysfunction caused to cells by exposure to radiation.¹⁶ Haeri SA1, Rajabi H, Fazelipour S, Hosseinimehr SJ. “Carnosine mitigates apoptosis and protects testicular seminiferous tubules from gamma-radiation-induced injury in mice.” Andrologia. 2013 Nov 12. http://www.ncbi.nlm.nih.gov/pubmed/24215656 Specifically, the study found that carnosine protects against the cellular dysfunction caused by testicular cell exposure to gamma-irradiation, ultimately even restoring the ability of those same cells to produce sperm. That’s astounding, as are its implications for carnosine’s ability to protect against the cellular dysfunctions associated with simple aging–as well as its ability to restore function where it may have been lost.

Carnosine Benefits for Your Brain and Nervous System

Brain damage from reduced blood flow to the brain in infants from about three months before birth to one month after (hypoxia-ischemia brain damage or HIBD) is a major cause of mortality and morbidity in neonates. Currently, there is no effective therapy for HIBD. But studies published in the European Journal of Pharmacology show that carnosine can indeed reduce brain damage in such situations.¹⁷ Zhang H, Guo S, Zhang L, Jia L, et al. “Treatment with carnosine reduces hypoxia-ischemia brain damage in a neonatal rat model.” Eur J Pharmacol. 2014 Jan 23. pii: S0014-2999(14)00024-7. http://www.ncbi.nlm.nih.gov/pubmed/24463179 Coupled with previous studies that have demonstrated the neuroprotective role carnosine can play when it comes to adult brain damage, it’s not hard to see why carnosine supplementation has built a reputation as one of the best things you can do to reduce your chances of succumbing to Alzheimer’s disease and dementia.

In fact, it looks like carnosine offers the same kind of protection to every nerve cell in your body, not just brain cells. A study published in Current Eye Research found that carnosine can protect nerve cells in your eyes, for example, from damage caused by reduced blood flow to cells in the retina.¹⁸ Ji YS, Park JW, Heo H, Park JS, Park SW. “The Neuroprotective Effect of Carnosine (ß-Alanyl-l-Histidine) on Retinal Ganglion Cell Following Ischemia-Reperfusion Injury.”Curr Eye Res. 2013 Nov 8. http://www.ncbi.nlm.nih.gov/pubmed/24206188

And a study published in PLoS One found that carnosine’s ability to break up alpha-crystallin amyloid fibrils is most likely associated with carnosine’s ability to inhibit the amyloid induced cytotoxicity of human neuronal cells, thereby reducing cell deaths in your brain.¹⁹ Wu JW, Liu KN, How SC, Chen WA, et al. “Carnosine’s Effect on Amyloid Fibril Formation and Induced Cytotoxicity of Lysozyme.” PLoS One. 2013 Dec 11;8(12):e81982. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859581/ Amyloid diseases, including hemodialysis amyloidosis, type II diabetes, Parkinson’s disease, transmissible spongiform encephalopathies, Huntington’s disease, and Alzheimer’s disease, are all characterized by the formation of insoluble deposits (aka, amyloid fibrils) in certain tissues and organs. The bottom line is that a constant stream of studies now indicates that if you don’t want to take supplemental carnosine to “look” younger and live longer, you will absolutely want to take it to better your odds of avoiding Alzheimer’s and a whole host of other amyloid related diseases.

This echoes another study, also published in PLoS One, that suggested that carnosine could play an effective role against the formation of fibrils/aggregates of the amyloidogenic peptide fragment Aβ1-42, which is also a major hallmark of Alzheimer’s disease injury.²⁰ Aloisi A1, Barca A, Romano A, Guerrieri S, et al. “Anti-aggregating effect of the naturally occurring dipeptide carnosine on aß1-42 fibril formation.” PLoS One. 2013 Jul 3;8(7):e68159. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700870/

But again, it’s not just dementia. An analytical paper published in 2013 indicated that carnosine could play a role in protecting against a range of age related diseases of the nervous system such as Parkinson’s.²¹ Hipkiss AR. “Aging risk factors and Parkinson’s disease: contrasting roles of common dietary constituents.” Neurobiol Aging. 2013 Dec 4. pii: S0197-4580(13)00616-7. http://www.ncbi.nlm.nih.gov/pubmed/24388766 Keep in mind that aging is a known risk factor for Parkinson’s disease. Specifically, there is evidence that indicates that excessive carbohydrate (glucose or fructose) catabolism is a factor in causing the mitochondrial dysfunction seen in Parkinson’s. One consequence of this dysfunction is an increased production of methylglyoxal (MG), an advanced glycation end product. But carnosine can not only scavenge MG but can also influence some of the biochemical events (signal transduction, stress protein synthesis, glycation, and toxin generation) associated with Parkinson’s pathology.

Miscellaneous Carnosine Benefits

An article appearing in the Sep-Oct 2013 issue of Advances in Clinical and Experimental Medicine concluded that due to its antioxidant, protective, chelating, and anti-glycation activity, carnosine could be used to prevent and treat diseases such as diabetes, neurodegenerative diseases, diseases of the sense organs, and even cancers.²² Budzen S1, Rymaszewska J. “The biological role of carnosine and its possible applications in medicine.” Adv Clin Exp Med. 2013 Sep-Oct;22(5):739-44. http://www.advances.am.wroc.pl/pdf/2013/22/5/739.pdf It may also cure or alleviate many other disorders thanks to its wide spectrum of activity. The authors noted that carnosine is already used by athletes to achieve better results, due to its buffering feature, which contributes to the maintenance of the acid-base balance in the muscles. And they stated that future studies on the influence of carnosine on the human organism may lead to the therapeutic use of this dipeptide for many diseases, in addition to improving both amateur and professional athletes’ results.

On a different note, it has been proposed that human blood platelet monoamine oxidase (MAO) activity is a biological marker of vulnerability to a variety of psychiatric diseases. Its activity is significantly inhibited as a result of aging, thus increasing the risk of problems as we age. A study published in the Journal of Physiological Sciences found that this age-induced inhibition of platelet MAO-A activity is reversed in as little as 21 days following the application of sufficient dosages of carnosine.²³ Banerjee S1, Poddar MK. “Platelet monoamine oxidase-A activity and aging: effect of carnosine.” J Physiol Sci. 2013 Jul;63(4):279-85. http://www.ncbi.nlm.nih.gov/pubmed/23657886 The study concluded that these results suggest that carnosine withdraws the aging-induced inhibition of mammalian blood platelet MAO-A activity and restores its activity towards that observed in young mammalian blood platelets. It seems that carnosine pushes the clock on aging back anywhere and everywhere we look in the body.

Perhaps the best example to end with is another analytical paper published in the Chemistry Central Journal that noted that carnosine has contrasting but beneficial effects on cellular activity.²⁴ Hipkiss AR, Cartwright SP, Bromley C, Gross SR, Bill RM. “Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?” Chem Cent J. 2013 Feb 25;7(1):38. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602167/ As mentioned earlier, carnosine delays cellular senescence and rejuvenates cultured senescent mammalian cells. The paper then went on to explain that studies have now also confirmed that carnosine inhibits the growth of cultured tumor cells as well. Based on studies in several organisms, the authors speculated that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide’s influence on cellular ATP concentrations. Carnosine’s ability to reduce the formation of altered proteins after exposure to methylglyoxal (see three paragraphs above) and enhance the breakdown of aberrant polypeptides is indicative of its ability to help maintain protein integrity throughout the body.

What makes this paper so special is the breadth of its conclusions as they cover virtually every disease commonly associated with aging. Quoting from the paper:

“Furthermore, these dual actions might provide a rationale for the use of carnosine in the treatment or prevention of diverse age-related conditions where energy metabolism or proteostasis are compromised. These include cancer, Alzheimer’s disease, Parkinson’s disease and the complications of type-2 diabetes (nephropathy, cataracts, stroke and pain), which might all benefit from knowledge of carnosine’s mode of action on human cells.”

Using Carnosine

Some experts recommend using only 50-100 mg of carnosine a day. Others say that if you don’t take 1,000-1,500 mg a day it won’t work because your body metabolizes the first 500 mg or so.

The key here is that all these experts are ignoring the simple fact that different people need different amounts. For example:

• The older you get, the more you need.
• If you eat a mostly vegetarian diet, you need more.
• If you’re diabetic, or just have trouble with blood sugar, you need more.

Over time, I’ve found that most people will do best on 500-750 mg a day.

If you’re young and healthy and include meat in your diet, then 250 mg a day makes sense. As you get older, and if you’re starting to show signs of aging or glycation (such as cataracts or aging skin), then you’d want to think of increasing the dosage up to 1,000 mg a day — maybe even as high as 1,500 mg a day.

Safety

In studies, carnosine has been proven safe in amounts as high as 70, 80, or even 100 grams a day, although a small number of people have noticed some minor muscle twitching at doses as small as 1,000 mg. The bottom line is use what you need, and you won’t have any problems — only benefits.

Importance

Once you understand what carnosine does — once you understand the role it plays in preventing and potentially reversing all of the signs of old age in the body (and we’re talking about everything from wrinkled skin to cataracts to Alzheimer’s) — heck, once you understand the role it plays in extending life itself — then you’re left with the unmistakable conclusion that supplementing with carnosine may represent one of the single best things you can do to help “turn back your biological clock.”

Lipofuscin, the Fly in the Ointment

As important as carnosine is, there is a “gap” in its usefulness. It’s called lipofuscin.

Lipofuscin deposits as seen in heart muscle

Lipofuscin is the pigment commonly found in aging brains and in other tissue such as the skin (think liver spots). By itself, it is not dangerous. It is merely a byproduct of harmful reactions that have already taken place. For example, one of the byproducts of free radical damage and protein/aldehyde damage (both conditions that carnosine addresses) is lipofuscin.

When you supplement with carnosine, however, something different happens. The carnosine quickly binds with the aldehydes, preventing them from damaging the proteins in your body. The byproduct of this reaction is also lipofuscin. So once again, you have inactive lipofuscin compounds, but this time as the result of PREVENTING protein damage. In a sense, with carnosine, you trade protein damage for lipofuscin.

Again, by itself, lipofuscin is not harmful. However, if enough of it accumulates over time (and this process is accelerated when you supplement with carnosine), it can interfere with proper cellular and organ functions. So, the bottom line is that however it is produced (as a result of protein damage, or as the result of taking sacrificial carnosine to prevent protein damage), you want to minimize it. Which leads us to a discussion of DMAE and Acetyl-L-Carnitine.

DMAE (Dimethylaminoethanol)

By any definition, DMAE is the perfect complement to carnosine in an anti-aging formulation. First, it reinforces carnosine’s own anti-aging properties. Then, it provides a whole series of complementary benefits of its own.

Also referred to as deanol and centrophenoxine (technically an ester of DMAE), dimethylaminoethanol is a naturally-occurring nutrient found in fish that enhances acetylcholine synthesis. Adequate levels of acetylcholine are important for proper memory function. Normally found in small amounts in our brains, DMAE has been shown to remarkably enhance brain function when used as a supplement (taken as laboratory produced DMAE bitartrate) in clinical studies.²⁵ Danysz A, Smietanski J, Panek W. “The influence of 2-dimethylaminoethanol (DMAE) on the mental and physical efficiency in man.” Act Nerv Super (Praha). 1967 Nov;9(4):417. http://www.ncbi.nlm.nih.gov/pubmed/5612961

DMAE Reinforces Carnosine

One of the prime actions of DMAE is that it flushes accumulated lipofuscin from your body — from the neurons in your brain, from your skin, and from all other organs.²⁶ Dylewski DP, Nandy S, Nandy K. “Effects of centrophenoxine on lipofuscin in the retinal pigment epithelium of old mice.” Neurobiol Aging. 1983;4(1):89-95. http://www.ncbi.nlm.nih.gov/pubmed/6410295 , ²⁷ Riga S, Riga D. “Effects of centrophenoxine on the lipofuscin pigments in the nervous system of old rats.” Brain Res. 1974 Jun 7;72(2):265-75. http://www.ncbi.nlm.nih.gov/pubmed/4151704 It also complements carnosine in that DMAE on its own has been shown to inhibit and reverse the cross-linking of proteins and extend lifespan.²⁸ Nagy I, Nagy K (1980). “On the role of cross-linking of cellular proteins in aging.” Mechanisms of Ageing and Development. 14 (1–2): 245–51. http://www.ncbi.nlm.nih.gov/pubmed/7206814

Many Baby Boomers have heard of the anti-aging results that Romanian scientist, Ana Aslan, achieved using something called GH3, or procaine. What most people do not know is that GH3 breaks down in the body to form DMAE (after first metabolizing into DEAE) and PABA. In other words, DMAE is the key active component in Ana Aslan’s anti-aging formula.

Numerous scientific studies now show that DMAE can help:

• Increase both acetylcholine levels and RNA levels in the brain²⁹ Malanga G, Aguiar MB, Martinez HD, Puntarulo S. “New insights on dimethylaminoethanol (DMAE) features as a free radical scavenger.” Drug Metab Lett. 2012 Mar;6(1):54-9. http://www.ncbi.nlm.nih.gov/pubmed/22300295
• Increases intelligence³⁰ Danysz A, Smietanski J, Panek W. “The influence of 2-dimethylaminethanol (DMAE) on the mental and physical efficiency in man.” Act Nerv Super (Praha). 1967 Nov;9(4):417. http://www.ncbi.nlm.nih.gov/pubmed/5612961
  • Stimulate mental activity
  • Increase attention span
  • Increase alertness
  • Improve learning and memory
• Increase energy levels
• Provide a mild, safe tonic effect
• Stimulate the central nervous system
• Relieve anxiety
• Elevate mood in general
• Alleviate behavioral problems and hyperactivity associated with Attention Deficit Hyperactivity Disorder³¹ Lewis JA, Young R. “Deanol and methylphenidate in minimal brain dysfunction.” Clin Pharmacol Ther. 1975 May;17(5):534-40. http://www.ncbi.nlm.nih.gov/pubmed/1092513
• Increase motivation and reduce apathy in persons suffering from depression
• Induce sounder sleep
• Over time reduce the amount of sleep required by about 1 hour per night
• Intensify dreams tremendously and cause them to become more lucid.³² Sergio W. “Use of DMAE (2-dimethylaminoethanol) in the induction of lucid dreams.” Med Hypotheses. 1988 Aug;26(4):255-7. http://www.ncbi.nlm.nih.gov/pubmed/3173167 (Even more so when you take it along with a large dose of phosphatidyl choline — a key component of lecithin)
• Increase willpower
• Decrease the incidence and severity of hangovers in people who consume excessive amounts of alcohol

DMAE Is Safe

Clinical studies of DMAE have used up to 1,600 mg per day with no reports of side effects. In some cases, some people may experience slight headaches, muscle tension, or insomnia if they take too much too soon.

These effects are easily eliminated if intake is reduced and then gradually increased. Although there is no direct connection, many manufacturers recommend that women who are pregnant or breast-feeding, or anyone who suffers from convulsions, epilepsy, or seizure disorders, and people with manic-depressive illness should avoid using DMAE.

This is probably more of a legal issue than a medical issue.

Acetyl-L-Carnitine

Like DMAE, acetyl-L-carnitine is a perfect complement to L-carnosine.

Although your body can synthesize L-carnitine in the liver, it depends on outside sources (meat being a primary source) to fulfill its requirements. This can present a problem for vegetarians since L-carnitine performs several key functions in the human body. For one, it can improve the functioning of the immune system by enhancing the ability of macrophages to function as phagocytes. And it can improve the functioning of muscle tissue. In fact, it has been shown to increase running speed when given prior to exercise. It also plays a major factor in cellular energy production by shuttling fatty acids from the main cell body into the mitochondria (the cell’s energy factories) so that the fats can be oxidized for energy. Without carnitine, fatty acids cannot easily enter the mitochondria.

There is, however, a specialized form of L-carnitine known as acetyl-L-carnitine (ALCAR) that is produced in the body and is often deficient even in meat eaters and that performs virtually all the same functions — but better. For example, in terms of cellular energy production, in addition to shuttling fatty acids into cell mitochondria, ALCAR provides acetyl groups from which Acetyl-Coenzyme A (a key metabolic intermediate) can be regenerated, thereby facilitating the transport of metabolic energy and boosting mitochondrial activity. But beyond that, the addition of the acetyl group makes ALCAR water soluble, which enables it not only to diffuse easily across the inner wall of the mitochondria but also to cross all cell membranes more easily. In other words, ALCAR reaches parts of the body where L-carnitine cannot go. In particular, ALCAR readily crosses the blood/brain barrier, where it provides several specialized neurological functions. For example, it can:

• Facilitate both the release and synthesis of acetylcholine, a key brain biochemical.
• Increase the brain’s levels of choline acetyltransferase (the enzyme responsible for the synthesis of acetylcholine)³³ Ferreira GC, McKenna MC. “L-Carnitine and Acetyl-L-carnitine Roles and Neuroprotection in Developing Brain.” Neurochem Res. 2017 Jun;42(6):1661-1675. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5621476/
• Enhance the release of dopamine and improve the binding of dopamine to dopamine receptors³⁴ Ferreira
• Protect the neurons of the optic nerve and the occipital cortex of the brain³⁵ Ferreira

In addition, studies have shown that acetyl-L-carnitine can inhibit the deterioration in mental function associated with Alzheimer’s disease and slow its progression.³⁶ Carta A, Calvani M, Bravi D, Bhuachalla SN. “Acetyl-L-carnitine and Alzheimer’s disease: pharmacological considerations beyond the cholinergic sphere.” Ann N Y Acad Sci. 1993 Sep 24;695:324-6. http://www.ncbi.nlm.nih.gov/pubmed/8239306 Part of this is a result of its ability to shield neurons from the toxicity of beta amyloid protein. As a result:

• ALCAR improves alertness in Alzheimer’s patients.
• Improves attention span.
• And it increases short term memory.

Through its action on dopamine (a chemical messenger used between nerve cells) and dopamine receptors, ALCAR seems to play a major role in preventing and/or minimizing the symptoms of Parkinson’s disease.³⁷ Singh S, Mishra A, Mishra SK, Shukla S. “ALCAR promote adult hippocampal neurogenesis by regulating cell-survival and cell death-related signals in rat model of Parkinson’s disease like-phenotypes.” Neurochem Int. 2017 Sep;108:388-396. http://www.ncbi.nlm.nih.gov/pubmed/28577987

• ALCAR enhances the release of dopamine from dopaminergic neurons and improves the binding of dopamine to dopamine receptors.
• ALCAR retards the decline in the number of dopamine receptors that occurs as part of the normal aging process and (more rapidly) with the onset of Parkinson’s disease. In fact, many researchers believe that Parkinson’s may be caused by a deficiency of dopamine.
• And ALCAR inhibits tremors.

And acetyl-L-carnitine may even play a role in helping with MS.

• ALCAR inhibits (and possibly reverses) the degeneration of myelin sheaths

But most of all, ALCAR just helps slow down the aging process of the brain.

• ALCAR retards the inevitable decline in the number of glucocorticoid receptors that occurs with aging.³⁸ Patacchioli FR, Amenta F, Ramacci MT, Taglialatela G, et al. “Acetyl-L-carnitine reduces the age-dependent loss of glucocorticoid receptors in the rat hippocampus: an autoradiographic study.” J Neurosci Res. 1989 Aug;23(4):462-6. http://www.ncbi.nlm.nih.gov/pubmed/2769802
• It retards the age-related deterioration of the hippocampus.³⁹ Singh
• It retards the inevitable decline in the number of nerve growth factor (NGF) receptors that occurs as we age.
• It stimulates and maintains the growth of new neurons within the brain (both independently of NGF and as a result of preserving NGF receptors) and helps to prevent the death of existing neurons.⁴⁰ Singh
• ALCAR protects the NMDA (N-methyl-D-aspartate) receptors in the brain from age-related decline.⁴¹ Robinson BL, Dumas M, Cuevas E, et al. “Distinct effects of ketamine and acetyl L-carnitine on the dopamine system in zebrafish.” Neurotoxicol Teratol. 2016 Mar-Apr;54:52-60. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924529/ NMDA receptor channels play an important role in synaptic plasticity and synapse formation, which underlies memory, learning, and the formation of neural networks during development in the central nervous system.
• ALCAR inhibits the excessive release of adrenalin in response to stress and inhibits the depletion of luteinising hormone-releasing hormone and testosterone that occurs as a result of excessive stress.
• And ALCAR enhances the function of cytochrome oxidase, an essential enzyme of the Electron Transport System.

The mind boosting effect of acetyl-L-carnitine is often noticed within a few hours — or even within an hour — of supplementing. Most people report feeling mentally sharper, having more focus, and being more alert. Some find a mild mood enhancement. More specifically:

• ALCAR improves learning ability along with both short term and long-term memory.⁴² Singh S, Mishra A, Srivastava N, Shukla R, Shukla S. “Acetyl-L-Carnitine via Upegulating Dopamine D1 Receptor and Attenuating Microglial Activation Prevents Neuronal Loss and Improves Memory Functions in Parkinsonian Rats.” Mol Neurobiol. 2018 Jan;55(1):583-602. http://www.ncbi.nlm.nih.gov/pubmed/27975173
• It improves mood by 53% and could potentially work as a rapid acting antidepressant.⁴³ Chiechio S, Canonico PL, Grilli M. “l-Acetylcarnitine: A Mechanistically Distinctive and Potentially Rapid-Acting Antidepressant Drug.” Int J Mol Sci. 2017 Dec 21;19(1). pii: E11. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795963/
• It both improves the quality of and reduces the need for sleep.
• It improves verbal fluency.⁴⁴ Passeri M, Iannuccelli M, Ciotti G, et al. “Mental impairment in aging: selection of patients, methods of evaluation and therapeutic possibilities of acetyl-L-carnitine.” Int J Clin Pharmacol Res. 1988;8(5):367-76. http://www.ncbi.nlm.nih.gov/pubmed/3229874
• And ALCAR improves hand eye coordination by some 300-400%.⁴⁵ Lino A, Boccia M, Rusconi A, Bellomonte L, Cocuroccia B. “Psycho-functional changes in attention and learning under the action of L-acetylcarnitine in 17 young subjects. A pilot study of its use in mental deterioration.” Clin Ter (Italy). 1992;140:569-573. http://www.ncbi.nlm.nih.gov/pubmed/1638856

Acetyl-l-carnitine is Safe

A study on L-carnitine has some people worried about using supplements that contain acetyl-l-carnitine. There is no reason to be concerned for a number of reasons.
First, this was a limited study ONLY involving 6 people. In fact, the primary data came from mice genetically engineered to have heart disease. Second, acetyl-l-carnitine is not L-carnitine. Although they are related, they are not the same substance; they are different molecules. They are broken down differently, used differently, and work in different areas of the body. Third, thanks to media scare headlines, the important findings of the study have been misinterpreted. For more information, check out: https://jonbarron.org/heart-health/acetyl-l-carnitine-supplements-and-heart-disease

Oh, and yes, acetyl-L-carnitine helps flush lipofuscin from the body — especially from the brain.⁴⁶ Amenta F, Ferrante F, Lucreziotti R, Ricci A, Ramacci MT. “Reduced lipofuscin accumulation in senescent rat brain by long-term acetyl-L-carnitine treatment.” Arch Gerontol Geriatr 1989 Sep-Oct;9(2):147-53. http://www.ncbi.nlm.nih.gov/pubmed/2589915

The Longevity Bottom Line

Ponce de Leon

Based on everything we know, supplementing with a combination of L-carnosine, DMAE, and acetyl-L-carnitine is one of the simplest, most effective, and safest steps you can take to help turn back the clock and optimize your health. For now, it’s the closest thing to Ponce De Leon’s Fountain of Youth. I’ve personally been taking my own version of this formula for the last 18 years.
Note: a number of people have been writing in lately asking about using beta alanine to boost carnosine levels to experience carnosine’s benefits. And yes, alanine is one of the two peptides, along with histidine, that combine to make up carnosine. And yes, if you supplement with beta alanine, your body will use it to raise carnosine levels in your body. The problem is that it’s not very efficient.   According to a review of the current literature published in the Jan 2010 issue of Nutrients, you need to supplement with 4.8 to 6.4 grams of beta-alanine a day to significantly increase muscle carnosine levels.⁴⁷ Julie Y. Culbertson, Richard B. Kreider, Mike Greenwood, and Matthew Cooke. “Effects of Beta-Alanine on Muscle Carnosine and Exercise Performance:A Review of the Current Literature.” Nutrients. Jan 2010; 2(1): 75–98. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257613/ Using carnosine supplements is far more efficient.

Still interested in more information on this topic? Review the following Newsletters:

• Anti-Aging Medical Discovery
• Nature of Aging, Part One
• Nature of Aging, Part Two
• Nature of Aging, Part Three
• Nature of Aging, Part Four