The anticipated demographic shift to an exponentially growing elderly population with increased morbidity poses the greatest challenge to society in history. This challenge raises a key scientific research question: Can we enhance human health span with the ever-increasing life expectancy resulting from advances in healthcare to prevent premature mortality? Aging is now the dominant risk factor for many degenerative disorders, for which mechanisms and dietary or environmental modulators remain poorly studied. The progressive increase in healthcare costs for non-communicable conditions and the rise in morbidity and mortality with advanced age is promoted by the cumulative bioenergetic burden upon the target population by the Western diet rich in sugar, fat, and salt. An imbalance between NO and SOR has been demonstrated in metabolic diseases such as diabetes and obesity. Antioxidant protection can determine health. Nutrition is decisive in determining health and healthcare costs. Precision nutrition, specific food, and biomatrix supplementation have been proposed to improve health by supplying sufficient macro and micronutrients. Adaptation and aging can be the opposite outcomes of dynamic developmental plasticity. The discovery and development of effective supplements containing amino acids and antioxidants that can restore and improve health even at an advanced age is a rapidly developing field of applied biosciences. Aging can be seen as a process of internal desynchronization induced by stress and aberrant-signaling-induced senescence and the concurrent loss of bioenergetic potential with a depletion of resources to prevent degenerative changes. Supplementation can maintain or even improve human health.

1. Adaptation and Aging

Lifetime exposure to high glucose and free fatty acid levels induces cumulative toxicity that limits adaptational and developmental plasticity. Premature aging and disease can result from nutrition rich in calories but poor in nutrients and natural agents. Supplementation rich in certain amino acids switches the metabolism to enhanced activity, efficacy, and oxidative phosphorylation capacity that improves mitochondrial redox regulation, inducing antioxidant adaptation by retrograde trophic pro-survival signaling. Since caloric restriction is often associated with malnutrition in humans, only bioenergetic agents such as the mitogenic and mitotrophic amino acids glutamine, proline, and arginine, which are abundantly present in proteins and peptides from pulses, grains, or collagen, can significantly improve the metabolism of mitochondria and stimulate their signaling. These amino acids are a real option to extend the human health span substantially. L-arginine and L-arginine-rich proteins or peptides can supply the necessary nutrients to reduce glycemic load, insulin resistance, and lipotoxicity by facilitating and enhancing fat oxidation and reducing glucose accumulation. Bioenergetic agents such as L-arginine and related amino acids have positive health effects, as demonstrated in the target population. These supplements induce bioenergetic stimulation, antioxidant protection, and ubiquitous regeneration that improve, restore, and maintain gut, skin, and joint health. The synergistic effects of this unique L-arginine-rich blend with antioxidant agents of high bioenergetic potency are discussed in the context of easy-to-handle approaches in supplementation aimed at improving, regaining, or maintaining health by improving the diet of the target population.

2. Nutrition and Health

Food and supplementation can be a decisive factor in maintaining health during aging and stress or enhanced demand for protective nutrients. Recent research indicates that a high intake of soy, pea, and pumpkin, rich in arginine, proline, and glutamine, can limit carbohydrate and fat toxicity associated with the Western diet and its predominant arginine-poor animal protein content. The use of amino acids like L-arginine together with the synergistically acting B vitamins, folate, vitamin B6, and vitamin B12, in preparations of premium quality and natural origin, opens up new perspectives in establishing a molecular, metabolic medicine that enables prevention, therapy, and rehabilitation for improving, maintaining, and restoring the health of older adults. Antioxidant protection and health-span extension seem to be possible through such an innovative approach as using amino acids and vitamins to enhance trophic retrograde NO signaling and thus life- and health-span. This review reveals how a holistic strategy employing amino acids like arginine combined with other nutrients can reverse chronic degenerative changes and trigger adaptive reactions and repair processes that restore regeneration via redox regulation and antioxidant protection. Novel, innovative approaches using highly sophisticated supplementation protocols have revealed the molecular mechanisms and physiological mediators of viability and survival that enable the organism to cope with internal and external stressors. All molecular mediators that induce such adaptive plasticity act as mitochondrial metabolism modifiers to increase trophic support through the enhanced supply and more efficient use of bioenergetic resources. The aim and goal of these approaches are to promote human fitness and health. The universal bioenergetic decline as a hallmark of stress and senescence can be corrected through supplementation-dependent mitochondrial support that restores metabolic control mechanisms essential to regeneration and repair.

3. Say NO to Aging

Aging is often associated with increased adiposity and altered reduced muscle mass or sarcopenia, including increased ectopic fat stores such as visceral, hepatic, and intermuscular fat, The age-dependent increase in asymmetric dimethylarginine (ADMA) levels and the upregulation of L-arginine depletion through enhanced arginase activity are the primary factors contributing to the alteration of the L-arginine/nitric oxide (NO) pathway associated with insulin resistance and endothelial dysfunction. These findings help explain the profound effects of precision supplementation, which involves an enhanced supply of L-arginine and other bioenergetic agents, in restoring metabolic control and reducing insulin resistance and lipotoxicity associated with enhanced superoxide anion radical and peroxynitrite formation in older adults. Currently, numerous clinical studies are being conducted to ensure that L-arginine supplementation and L-arginine-rich food can restore redox regulation in the elderly target population. Aging leads to decreased arginine: ADMA ratio and the nitric oxide: superoxide ratio, resulting in oxidative stress, inflammation, and degenerative changes that harm development and health. Supplementation with amino acids such as L-arginine and L-arginine-rich food through certain peptides and proteins can restore a healthy arginine: ADMA ratio.

Recent research confirms the crucial roles of metabolic pathways in regulating and determining human health. The ultimate goal is to explore new avenues that enable active living and healthy aging by preserving fitness throughout life. Upregulating nitric oxide bioavailability can prevent premature aging and neurodegeneration. Boosting the nitrate-nitrite-nitric oxide pathway improves gastrointestinal, cardiovascular, metabolic, and cognitive performance. Vegetables rich in nitrate, like spinach and beetroot, are a good source of nitric oxide, with beneficial effects on cardiovascular health and a lower risk of cardiovascular disease.

L-arginine has potent health-protecting effects, and its beneficial cardiovascular effects are well-established. The age-dependent decline of tryptophan in the brain is associated with toxic kynurenine formation, which impairs nitric oxide formation and leads to insulin resistance and metabolic syndrome.

Supplementation with L-arginine and B vitamins can stop the vicious cycle of oxidative stress and damage. Selectively increasing tryptophan levels through L-arginine or L-arginine-rich food can boost nitric oxide bioactivity and bioavailability. This approach can target elevated blood pressure and improve cardiovascular health. Nitric oxide (NO) can be cytotoxic at high concentrations, but its antioxidant effects typically prevail. Moderate consumption of vegan L-arginine-rich proteins may be beneficial for individuals with kidney problems. Older adults and those with cardiovascular and cardiometabolic diseases have an enhanced need for L-arginine and L-arginine-rich proteins to restore and sustain a healthy NO supply.

L-arginine plays a decisive role in preserving brain health, preventing cognitive impairment, and maintaining high NO levels for healthy aging. Aging and age-related cardiovascular diseases lead to arginine and tryptophan depletion, impairing neurovascular coupling. L-arginine and L-tryptophan determine disease development and progression. Supplementation with L-arginine and L-arginine-rich food assures sufficient NO synthesis, neutralizing the age-dependent accumulation of ADMA and the enhanced formation of superoxide anion radicals.

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From what we know, Plato, the great thinker that he was, was clearly already practising preventative health measures, a key aspect of longevity, in his daily life. But what is longevity? In this blog post we will be explaining what longevity is, choices that can be made with longevity in mind and, most importantly, why we should care…

What is Longevity?

The Cambridge Dictionary definition of ‘longevity’ is ‘living for a long time’. Perhaps unsurprisingly, in modern medical academia, research into the extension of a human lifespan is referred to as ‘longevity’ (or longevity research). So how is this different to the rest of medicine?

Modern medical advances have largely been the cause of the modern extension of average life expectancy, addressing health conditions that have previously had high mortality rates and considerably lessening child mortality rates.[4] Put short, as the length of a human lifespan has increased – the limit has not. As noted by Harvard Professor of Genetics Dr. David Sinclair in his landmark book ‘Lifespan: Why We Age and Why We Don’t Have To’, we have conceded that mortality is a reality and instead turned medicine to other directions. Most particularly, our medicine has been turned toward the treatment of diseases that afflict us as we age – ‘making mortality a medical experience’.[5]

The main issue with how we address illness, despite the amazing work done by the medical researchers who dedicate their lives to this cause, is that simply stopping one disease does not make it less likely that a person will not be afflicted, or perhaps killed, by another. But – and there is a but – through longevity research we can not just pursue cures for individual diseases. We can instead address a shared underlying factor behind them: Aging.

So why should we care about Longevity?

If you’ve read the above but, understandably, thought that this just sounds like the beginning of a promising development for future generations then you are easily forgiven. Myths about the extension of life have existed for thousands of years and still pervade modern culture today – you’d be hard pressed to find someone who doesn’t know about the fountain of youth or the holy grail. Yet through modern research, it is increasingly probable that we will find a way to extend the lifespan of a human life – and far, far sooner than you would think.

It is already thought that someone who is currently alive today will live a longer lifespan than has ever been recorded in human history. The professor emeritus of developmental biology at Stanford, Stuart Kim, has stated that there are people alive today who will live to 200 – and has even made a bet with a colleague on the matter. This bet will be worth around $1 billion in 2150… if either of them live to collect it.[6] Some would say this figure itself is optimistic but Dr. Sinclair has put across a different theory. He believes that we could potentially live forever. But whatever the upper limit, it is obvious that the leading minds of longevity research are increasingly convinced that it is possible for humans to live far longer than the time we have believed is allotted to us.

To live forever…

At present however, until the coming gerontological breakthrough, longevity-minded individuals are acting to ensure that they benefit from the coming developments – and live long enough to benefit from each next innovation in the field. This strategy has been described as seeking ‘bridges to immortality’ by the futurist Ray Kurzweil.[7] This involves utilising preventative health choices to pre-empt health conditions, with the theory that if one is able to extend their lifespan for an additional twenty years then they will still be alive to benefit from these longevity treatments.

Another aspect of the longevity movement is the personal effort to increase what most of us would describe as ‘the good years’. In other words, our healthy and energetic years. It was mentioned above that mortality has been made a medical experience. As we get older, and feel our mortality, we require constant visits to the hospital to deal with medical afflictions that have developed during our lives and the myriad newer health problems that develop alongside or due to these comorbidities.[8] In short, a person who does not die of acute illnesses, such as infections, and survives with chronic illnesses is more likely to develop additional chronic illnesses.[9]

…Or, to stay forever young…

So, a significant part of the longevity movement is encouraging individuals to take ownership of their own health – being an active subject caring for themselves, not a passive subject treated by doctors when a problem arises. Longevity is about the prevention of aging, which is the cause of diseases and pre-empting problems before they arise (as opposed to diagnosis and treatment of chronic diseases).

Through this method, we can have a better and longer lifespan and, with the best hope, live to see gerontological advances that can prolong our lives yet further. Longevity in practice is about finding behavioural measures, healthy choices, that work for you so you can build a lifestyle around them – and by doing so prevent or lessen the severity of health problems that you may have in the future. Simply, acting now to prolong your best years and dodge prolonged hospital visits for as long as possible.

To find out more about how to live with longevity in mind, check out the links below:

• Practising longevity in your youth (18-30).
• Practising longevity in your middle age (30-60).
• Practicing longevity in later life (60+).

In closing

The earlier you start making the choice to build longevity-minded habits into your lifestyle, the longer and healthier you will likely live. Leading experts in the medical field already believe that living a lifespan with a length previously unrecorded is within reach. The longer we can remain healthy, the longer we can live. Plus, if aging breakthroughs arrive while we are still healthy, it is very possible that we may live energetic lives well past 100 – potentially even living young forever. By reading this blog post, you’re already making proactive steps toward building healthy habits into your life and are likely researching healthy choices that are available for you.

Check out the links above for some basic suggestions on how to live life with longevity in mind. Also make sure to keep up to date with our blog here and sign up to all of the NOMIX social channels (Twitter and Telegram) for more news about longevity.

[1] Some might think it strange for a blog post on the topic of longevity and how to maximise it to mention Plato, given that one of his famous quotes is ‘attention to health is life’s greatest hinderance’, however, Plato actually means that being forced to pay attention to your health – through poor health – is a hinderance.

[2] Diogenes Laërtius, Life of Plato, II

[3] Passarino, G., De Rango, F., & Montesanto, A. (2016). Human longevity: Genetics or Lifestyle? It takes two to tango. Immunity & ageing : I & A, 13, 12. https://doi.org/10.1186/s12979-016-0066-z

[4] I write ‘largely’, as the part played by an increased, reliable food supply and clean water has also played a significant part in increasing human lifespans.

[5] Sinclair, D., PhD & LaPlante, M.D., Lifespan: Why We Age- and Why We Don’t Have To’, (2019), pXVII.

[6] Taylor, G. (2017). Scientist thinks that the world’s first 200-year-old person has already been born. Norway Today, 23^rd March 2017. https://norwaytoday.info/everyday/scientist-thinks-worlds-first-200-year-old-person-already-born/

[7] Adler, R. (2010). Ray Kurzweil: Building bridges to immortality. New Scientist, December 27^th 2010. https://www.kurzweilai.net/building-bridges-to-immortality

[8] ‘Comorbidity’ refers to other health problems that a patient can have, when talking about a health problem.

[9] Divo, M. J., Martinez, C. H., & Mannino, D. M. (2014). Ageing and the epidemiology of multimorbidity. The European respiratory journal, 44(4), 1055–1068. https://doi.org/10.1183/09031936.00059814

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Since most theories in this field, s.a. the disrepair accumulation theory of aging, postulate that the potential for longevity of an organism is positively correlated to its structural complexity, and we human beings belong to the most complex mammals, we are widely considered to have a naturally limited longevity due to aging, which results in a life expectancy of 80-85 years for millennials in developed countries.

The United Nations has made projections up to 2300, at which point it projects that life expectancies in most developed countries will be between 100 and 106 years and still rising, though more and more slowly than before. Gaps in life expectancy between rich and poor countries may well not exist in the future, due to the exchange of technology and the industrialization and development of poor countries, similarly to the way life expectancies between rich and poor countries have already been converging over the last 60 years as better medicine, technology, and living conditions became accessible to most people. 

“The possible existence of a hard upper limit, a cap, on human lifetimes is hotly debated,” write Léo Belzile and coauthors in a paper to appear in Annual Review of Statistics and Its Application. “It is sustained and widespread interest in understanding the limit, if there is any, to the human lifespan.” Their own re-analysis of previously incorrectly analyzed data on extreme lifetimes indicates that any longevity cap would be at least 130 years and possibly exceed 180. And some datasets, the authors report, “put no limit on the human lifespan.” These analyses “suggest that the human lifespan lies well beyond any individual lifetime yet observed or that could be observed in the absence of major medical advances.”

However, recent increases in the rates of lifestyle diseases, such as obesity, diabetes, hypertension, and heart disease, may eventually slow or reverse this trend toward increasing life expectancy in the developed world. 

The post What Is Longevity? appeared first on NOMIX.

Links  
Weapon fragments in bowhead whales
Rapamycin extends lifespan in mice
Targeting Aging with Metformin (TAME) Trial
Metformin improves healthspan and lifespan in mice
Metformin reduces all-cause mortality
Reprogramming to restore vision
DNA methylation age
Genome-wide methylation profiles & human aging rates
Reversal of epigenetic aging in humans
Danish twins study

The post Why Do We Age? appeared first on NOMIX.

In this podcast episode, Andrew Huberman and David Sinclair discuss the cellular and molecular mechanisms of aging and what we all can do to slow or reverse the aging process. They discuss (intermittent) fasting and supplementation with Resveratrol, Metformin, and NMN.

They also discuss the use of caffeine, exercise, cold exposure, along with food choices for offsetting aging and promoting autophagy, the process of clearing the organism of dead cells. And they discuss the key blood markers everyone should monitor to determine their biological versus chronological age.

It rarely happens that top scientists talk in easily understandable words and provide such a wealth of useful advice. We therefore strongly recommend listening to or even watching this podcast episode – these two hours might belong to the best investment of your valuable time, ever! Since – who does not want to stop aging?!

Enjoy!

The post Why We Age, And Why We Don’t Have To appeared first on NOMIX.