While science and medicine have long relegated age-related chronic diseases to the realm of the inevitable, a growing body of research indicates that we can change how we age! The diet and lifestyle choices we make every day have a significant impact on the aging process and can influence whether we age gracefully or succumb to chronic disease. Read on to learn how you can take control of the aging process and stay youthful and healthy for years to come, with the help of strategic nutrition interventions.
What should you eat for a longer lifespan? Check out this article from nutritionist Lindsay Christensen to find out. #nutrition #optimalhealth #wellness
- 1 A Primer on the Nine Hallmarks of Aging
- 1.1 1. Genomic Instability
- 1.2 2. Telomere Attrition
- 1.3 3. Epigenetic Alterations
- 1.4 4. Loss of Proteostasis
- 1.5 5. Deregulated Nutrient Sensing
- 1.6 6. Mitochondrial Dysfunction
- 1.7 7. Cellular Senescence
- 1.8 8. Stem Cell Exhaustion
- 1.9 9. Altered Intercellular Communication
- 1.10 Sirtuins Link Several Hallmarks of Aging
- 2 Inflammaging: A Cause and Effect of Aging
- 3 Six Steps to Achieving Optimal Nutrition for Healthy Aging
- 3.1 1. Say “Goodbye” to the Standard American Diet
- 3.2 2. Eat a Nutrient-Dense, Anti-Inflammatory Paleo-Template Diet
- 3.3 3. Support Your Microbiome
- 3.4 4. Improve Blood Sugar Stability
- 3.5 5. Try Fasting and Time-Restricted Feeding
- 3.6 6. Consider a Ketogenic Diet
- 4 How Dietary Protein and Glycine Impact Aging
- 5 Other Compounds that Support Healthy Aging: Carnosine and NAD Precursors
- 6 Nutraceuticals that May Help Slow Aging
A Primer on the Nine Hallmarks of Aging
In this article, we’ll cover six steps to optimal nutrition for healthy aging. But first, to better understand how we can use nutrition to attenuate the aging process, it is helpful to understand the processes that cause us to age. These processes can be distilled down into nine hallmarks of aging: (1)
- Genomic instability
- Telomere attrition, otherwise known as “telomere shortening”
- Epigenetic alterations, such as altered methylation
- Loss of proteostasis
- Deregulated nutrient sensing
- Mitochondrial dysfunction
- Cellular senescence
- Stem cell exhaustion
- Altered intercellular communication
The nine processes involved in aging are intricately interconnected, linked, and overlapping. While a discussion of these mechanisms could fill an entire article on its own, let’s briefly discuss each of these pathways in turn and then review how they interrelate with nutrition. The exciting aspect of modifying the aging process with nutrition is that because these processes are linked, nutrition interventions that alleviate one hallmark of aging may also beneficially impact other hallmarks.
1. Genomic Instability
Throughout our lifespan, the integrity of our DNA is continuously challenged by external agents, including ultraviolet light and environmental toxins, and internal factors such as DNA replication errors and reactive oxygen species generated as part of cellular metabolism. These factors cause a range of DNA alterations, including point mutations and chromosomal gains and losses, that irreversibly change the content of our genome and gene expression. Impaired gene expression causes cellular dysfunction and jeopardizes the function and well-being of the entire body. This is especially salient when DNA damage impacts the function of stem cells, compromising their vital role in tissue repair. While our bodies harbor a complex network of DNA repair mechanisms for dealing with DNA damage, defects in these repair mechanisms also occur with age.
One of the main factors that impact the stability of our genome, and thus our gene expression, is our diet. While nutrition interventions may not reverse pre-existing genomic instability, optimal intake of nutrients involved in genomic stability and DNA repair, such as methylfolate and vitamin C, may help prevent the development of further genomic instability. (2, 3) The earlier you begin caring for your body with optimal nutrition, the more significant an impact you’ll have on the lifelong stability of your genome and on your longevity.
2. Telomere Attrition
Telomeres are regions of repetitive nucleotide sequences (nucleotides are the building blocks of DNA) found at the end of each chromosome in your body. They protect the chromosome ends from damage and prevent the chromosome from fusing with other chromosomes. During chromosome replication, an intrinsic part of cell replication, the enzymes that duplicate DNA cannot replicate the DNA all the way to the end of the chromosome; as a result, the chromosome is shortened with each replication. The region of the chromosome that is shortened with each replication, serving as a disposable “buffer,” is the telomere.
Telomere shortening, also referred to as “telomere attrition,” is a normal part of being a living, breathing human with replicating cells. However, telomeres are also particularly susceptible to age-related DNA damage and deterioration, and accelerated telomere attrition is a hallmark of aging. (4) Whether telomere attrition is a cause or an effect of aging remains to be fully explained. However, we do know that as we lose the protective “caps” on our chromosomes, our DNA becomes more susceptible to DNA damage, tying into our earlier discussion on genomic instability. Fortunately, research shows that telomere attrition is amenable to nutrition interventions and that it may be possible to prolong the lifespan of healthy telomeres with food. (5)
3. Epigenetic Alterations
While irreversible changes to the genome occur with aging (see “Genomic Instability”), epigenetic alterations also play a role in the aging process. Epigenetics is the study of changes in organisms caused by the modification of gene expression, rather than a revision of the genetic code itself. Methylation, modification of histones (the proteins around which DNA is wrapped), and chromatin remodeling are examples of epigenetic mechanisms.
Specific epigenetic “marks,” caused by the methylation process, are associated with aging. (6) These marks increase genomic instability and contribute to cellular senescence and mitochondrial dysfunction, demonstrating the interrelationships between the hallmarks of aging.
Several scientists, including Steve Horvath and Morgan Levine, have developed biochemical tests called “epigenetic clocks” that can be used to measure age based on DNA methylation levels. These tests detect areas of methylation in DNA and use that data to calculate one’s “biological age” or how old a person is on a physiological level. One’s biological age may be younger or older than one’s chronological age based on epigenetic factors such as diet, exercise, and sleep habits. Several direct-to-consumer tests, such as myDNAge and InsideTracker, are now available and can be used to approximate your biological age.
Modifiable lifestyle factors such as diet, exercise, and sleep are known to modify gene expression and may attenuate epigenetic changes that occur with age. (7, 8)
4. Loss of Proteostasis
The human body relies heavily on proteins to control various biological processes. Proteostasis (protein homeostasis) is the concept that a balanced network of biological pathways within cells regulates the biogenesis, folding, inter- and intracellular trafficking, and degradation of proteins in the body. When the proteostasis balance is lost, an excess of misfolded, dysfunctional, and toxic proteins is created while healthy, well-functioning proteins are depleted. Factors that contribute to loss of proteostasis include oxidative stress and impairment of protein degradation systems, such as autophagy.
Loss of proteostasis triggers the accumulation of misfolded proteins, many of which are involved in age-related diseases such as Alzheimer’s disease, Parkinson’s disease, and cataracts. Preclinical research suggests that nutritional interventions, such as fasting, promote healthy proteostasis and may inhibit the age-related accumulation of dysfunctional proteins. (9)
5. Deregulated Nutrient Sensing
Nutrient sensing refers to a cell’s ability to recognize and respond to fuel substrates such as glucose, fatty acids, and ketones. Upon recognizing these substrates, the cell activates signaling pathways that affect gene expression and countless other physiological processes. Three key nutrient sensing pathways include the insulin-like growth factor (IGF-1), mammalian target of rapamycin (mTOR), and adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways.
The IGF-1 pathway takes part in glucose sensing and is also involved in normal bone and tissue growth and development. IGF-1 shares a common genetic ancestry with insulin, an anabolic peptide hormone that allows our bodies to use glucose as fuel, among other functions. Meal-induced increases in insulin trigger IGF-1 production. It helps promote normal bone and tissue growth and development. Downregulation of IGF-1 inhibits cell proliferation and has been suggested as a target for slowing aging. However, the role between IGF-1 in aging is not clear-cut; while low serum IGF-1 predicts longevity, IGF-1 also decreases with age, and IGF-1 therapy has been found to improve some age-related diseases. (10)
The mTOR pathway is a central regulator of metabolism, lifespan, and aging in mammals. (11) It plays crucial roles in growth during childhood and adolescence, and in the growth and maintenance of muscle mass. However, excessive mTOR signaling is also linked to the development of age-related diseases such as type 2 diabetes, cardiovascular disease, and neurodegenerative diseases.
The AMPK pathway is a key cellular energy sensor and a master regulator of metabolism. (12) It is activated under conditions of nutrient scarcity (low glucose). It activates pathways that produce more adenosine triphosphate (ATP), and inhibits anabolic pathways that promote cell growth. AMPK is considered a pro-longevity pathway, in contrast to IGF-1 and mTOR.
While the effects of IGF-1, mTOR, and AMPK signaling on the body as they relate to nutrition are extremely complex, I’ve (greatly) simplified them here:
- Eating chronically, as many do in the modern-day Western world, chronically activates IGF-1 and mTOR. This sends signals to cells triggering them to continually grow and store energy, primarily as fat tissue. Conversely, the reparative, pro-longevity AMPK pathway is inhibited.
- While AMPK is pro-longevity, we do not want it to constantly be activated either. When AMPK is chronically activated, biosynthetic pathways needed to make hormones, cholesterol, and other vital molecules are impaired.
- What we want is a healthy balance between IGF-1, mTOR, and AMPK activity. In young people, this balance is maintained pretty effortlessly. However, the homeostatic balance is deregulated with age, contributing to age-related diseases such as type 2 diabetes and cardiovascular disease.
Research indicates that nutrition can be used to regulate nutrient sensing pathways, promoting healthy aging. (13) We will dive into this topic shortly.
6. Mitochondrial Dysfunction
Mitochondria are the “power plants” of our cells, where energy for fueling all the biochemical processes in our bodies is generated. Mitochondria also play critical roles in regulating metabolic health and inflammation. Mitochondrial dysfunction is implicated in the aging process. Dysfunctional mitochondria cannot produce sufficient energy for healthy cellular function, and whole-body health suffers as a result. (14)
7. Cellular Senescence
Cellular senescence is the process by which once-proliferating cells enter a state of stable cell cycle arrest. While cellular senescence is a normal part of human biology, limiting the replication of old and damaged cells, it occurs at an increased pace with aging. Excessive cellular senescence reduces the number of immune cells in the body, triggering “immunosenescence.” (15) Senescent cells also produce a “senescence-associated secretory phenotype,” secreting inflammatory mediators that damage neighboring cells and tissues.
Senolytic agents, or substances that inhibit cellular senescence, are being studied as potential therapies for aging. However, many natural compounds present in a nutrient-dense diet, such as resveratrol, may also arrest or delay cellular senescence. (16)
8. Stem Cell Exhaustion
Stem cells are cells within the body that have the potential to develop into many different types of cells. They serve as a repair system for the body, supplying new cells to replace old, damaged ones. Since stem cells are needed to regenerate tissues, a loss of stem cells promotes tissue aging. In fact, stem cell loss, also referred to as stem cell exhaustion, is thus a central factor in the aging process. (17) Nutritional strategies that stave off stem cell loss and promote the regeneration of healthy stem cells represent a promising avenue for facilitating healthy aging.
9. Altered Intercellular Communication
Aging changes how cells communicate with each other, causing systemic dysfunction in the endocrine, neuroendocrine, and neuronal systems. (18) Dysfunctional intercellular communication alters physiological function and contributes to processes such as inflammaging (more on this shortly).
Sirtuins Link Several Hallmarks of Aging
Sirtuins are a family of signaling proteins involved in metabolic regulation and longevity that are highly conserved throughout all kingdoms of life, including plants and animals. They act mainly as nicotinamide adenine dinucleotide (NAD)+-dependent deacetylases with a wide range of target proteins, removing acetyl groups from proteins such as histones and transcription factors, thereby affecting gene expression.
Sirtuins are multi-purpose proteins that link several hallmarks of aging, including genomic instability, epigenetic modifications, and nutrient sensing. Sirtuin activity supports healthy glucose homeostasis, which is essential for optimal nutrient sensing. Conversely, excessive IGF-1 and mTOR activity inhibit sirtuins. Sirtuins also mediate autophagy, a proteostasis-related process by which damaged proteins and organelles are targeted for degradation by lysosomes. (19, 20) Finally, sirtuins are also involved in stem cell biology and may help maintain a robust stem cell pool.
By modulating aging-related processes, sirtuin activity may confer protection against a range of age-related diseases, such as cardiovascular disease and neurodegenerative disease. Emerging research indicates that nutrition has a profound impact on sirtuins. Natural compounds that activate sirtuins (more on this shortly) are referred to as sirtuin-activating compounds (STACs).
Inflammaging: A Cause and Effect of Aging
While not included on the list of nine hallmarks of aging, the phenomenon of “inflammaging” is also a central component of the aging process. Inflammaging (inflammation + aging) refers to the chronic, low-level inflammation characteristic of aging. (21) Inflammaging sits at the confluence of multiple hallmarks of aging, linking cellular senescence with deregulated nutrient sensing and other age-related pathologies. Adverse changes in the gut microbiota may also contribute to inflammaging, suggesting that the gut microbiota may be an essential target for interventions designed to support healthy aging.
Clearly, the phenomenon of aging is an extremely complex process. While scientists are still sorting out all the intricacies of aging, what we know for sure is that diet and lifestyle have significant effects on how well you age. Nutrition is a powerful tool for supporting graceful aging and longevity. Let’s discuss some evidence-based nutrition strategies that can help you age with health, vitality, and grace.
Six Steps to Achieving Optimal Nutrition for Healthy Aging
1. Say “Goodbye” to the Standard American Diet
The first step in using nutrition to support healthy aging is to avoid processed, refined, and inflammatory foods. Chronic consumption of carbohydrate- and fat-rich processed foods impairs glycemic control, causing sustained elevations in insulin and IGF-1. A Western diet is also linked to DNA damage and inflammation, underlying factors in aging. (22)
Our diet and lifestyle choices have an outsized impact on our overall health and longevity. Eating nutrient-dense, whole foods (instead of the standard American diet), engaging in regular exercise (rather than remaining sedentary), and practicing stress management (instead of living in a state of chronic busyness) can all do wonders to improve your health and prevent or reverse the chronic diseases that can shorten your lifespan. But knowing that our habits impact our health often isn’t enough reason for us to change them—we have to feel truly motivated to do so. That’s where health coaches shine.
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2. Eat a Nutrient-Dense, Anti-Inflammatory Paleo-Template Diet
Once you’ve cut acellular carbohydrates, industrial seed oils, and processed foods out of your diet, it’s time to incorporate foods with a track record of supporting healthy aging. A Mediterranean diet, which provides a good template for an anti-inflammatory whole foods-based diet, has been found to slow down the progression of aging and inhibit the onset of frailty. (23) However, it does recommend a high intake of grains, which may not be ideal for many people. I, therefore, recommend a nutrient-dense, anti-inflammatory Paleo template for longevity.
Paleo Template Longevity Diet
- Non-starchy vegetables: Aim for three to four servings per day of non-starchy vegetables such as leafy greens, broccoli, cauliflower, Brussels sprouts, kale, bell peppers, asparagus, green beans, and artichokes.
- Starchy tubers and whole fruit: Starchy tubers, such as sweet potatoes and cassava, and whole fruit are nutrient-dense sources of carbohydrates that feed beneficial gut bacteria without triggering massive fluctuations in blood sugar and insulin release.
- Animal protein: Grass-fed beef, pastured poultry, wild game, wild-caught seafood, and eggs are highly bioavailable sources of protein and other nutrients that our bodies need to age gracefully, such as vitamin B12 and the omega-3 fatty acids EPA and DHA. However, for longevity, it is crucial to eat nose-to-tail, as this practice supports a balanced intake of amino acids; as I’ll discuss shortly, amino acid balance may be the “missing link” in studies suggesting that animal protein consumption is detrimental to aging.
- Healthy fats: Healthy fats such as extra virgin olive oil (EVOO), organic unrefined coconut oil, avocado oil and avocados, fresh nuts and seeds, and wild-caught seafood are anti-inflammatory additions to your longevity diet.
Gray-area foods that may or may not be suitable additions to your longevity diet, based on your digestive system health and other health conditions, are legumes, gluten-free grains, and dairy.
Milk products have insulinotropic effects and can potently activate IGF-1 signaling; as a result, daily consumption of dairy products may not be ideal from a longevity standpoint. Legumes and gluten-free grains, on the other hand, may be perfectly healthy additions to your diet if you can properly digest them and aren’t sensitive to some of the antinutrients they contain, such as lectins.
Must-Have Foods for Longevity
Finally, there are specific foods you should include in your diet for their science-backed anti-aging benefits:
- Green tea: In large population-based studies, green tea consumption is associated with healthy aging. (24) It may exert beneficial effects on aging by activating the AMPK pathway, destroying inflammatory senescent cells, and enhancing the differentiation of stem cells. (25, 26, 27)
- EVOO: EVOO is a pillar of the longevity-supporting Mediterranean diet. (28) Olive oil components, such as polyphenols, beneficially affect stem cell integrity and differentiation, upregulate AMPK and sirtuins, and exert senolytic effects on senescent cells. (29, 30, 31)
- Astaxanthin: Astaxanthin is a pinkish-orange pigment found in certain types of seafood, such as wild-caught salmon. (32) It is famous for its antioxidant effects, but emerging research indicates that its consumption may also support healthy aging by targeting defects in mitochondrial function.
- Curcumin: Curcumin, a bioactive compound found in bright orange turmeric root, may modulate the aging process, inducing the death of pro-inflammatory senescent cells by upregulating AMPK and sirtuins, and by inducing autophagy. (33)
- Sulforaphane: Sulforaphane, a sulfur-based phytochemical found in cruciferous vegetables, upregulates the antioxidant Nrf2 signaling pathway. This pathway may be involved in longevity due to its protective effects against cellular oxidative stress. (34, 35)
3. Support Your Microbiome
Research suggests that changes in the microbiome contribute to inflammaging and the overall aging process. (36) Dietary support for the microbiome, including probiotic-rich fermented foods and prebiotic foods such as garlic, onions, and apples, boosts anti-inflammatory gut bacteria and may promote healthier aging. (37)
4. Improve Blood Sugar Stability
Blood sugar control has profound effects on the aging process due to its impact on insulin signaling and the homeostatic balance between the IGF-1, mTOR, and AMPK signaling pathways. In fact, high serum glucose levels are associated with higher perceived age and familial longevity is linked to higher insulin sensitivity, and thus lower blood glucose. (38, 39)
One way to get insulin and blood sugar levels under control, and possibly slow the aging process, is to swap out refined carbohydrates for nutrient-dense carbs such as sweet potatoes and whole fruit. The amount of nutrient-dense carbohydrates you should eat depends on many factors, including your activity level and health goals. You can learn more about how to determine the macronutrient ratios that suit your needs in Chris’s article “How to Calculate Macronutrient Ratios that Work for You.”
5. Try Fasting and Time-Restricted Feeding
Fasting works through multiple pathways to enhance healthy lifespan. Research indicates that it alleviates many of the hallmarks of aging, including:
- Increases NAD, a cofactor for sirtuins, and thus sirtuin activity (40)
- Suppresses mTOR (41)
- Ramps up AMPK signaling (42)
- Activates stem cell renewal (43)
The duration of fasting needed to activate these processes in humans is currently unknown. However, a minimum of 24 hours is generally required to boost these processes in mice, which have a higher metabolism than humans. It is thus reasonable to assume that we may need to fast for multiple days at a time to achieve these more dramatic anti-aging health benefits.
Does the concept of multi-day fasting scare you away? If it does, no worries! Research suggests there are other “fasting-mimicking” practices that may help us achieve similar effects. Scientist Valter Longo’s fasting mimicking diet (FMD) is one such option. The FMD involves significantly reducing your total calorie intake for three to five days each month; after this three- to five-day period, regular eating habits are resumed for the remainder of the month. This constitutes one cycle of the FMD. The FMD cycles are continued until desired health results are achieved. In preclinical studies of the FMD, it has been found to reverse immunosuppression, a critical factor that contributes to aging. (44)
Other forms of fasting to consider are time-restricted feeding, alternate-day fasting, and intermittent fasting. Intermittent fasting, in a broad sense, refers to the process of voluntarily cycling between periods of fasting and non-fasting. One example of intermittent fasting includes engaging in a fast between dinner and breakfast the next day, for at least 13 hours. While intermittent fasting may not induce significant changes in processes such as cellular senescence and stem cell renewal, it has been found to improve metabolic health, a critical predictor of healthy aging. (45) Periodic alternate-day fasting, in which you fast every other day, is another option. Alternate-day fasting in humans has been found to improve both physiological and molecular markers of aging. (46) However, it is not a feasible or healthy long-term approach for most people.
6. Consider a Ketogenic Diet
Nutritional ketosis is another powerful dietary intervention that may attenuate the aging process, and the primary way to achieve nutritional ketosis is through a ketogenic diet.
How might a ketogenic diet and nutritional ketosis beneficially impact aging? In preclinical (animal) studies, a ketogenic diet has been found to boost intestinal stem cell renewal through the actions of ketone bodies on the intestinal stem cell pool. (47) Nutritional ketosis may also improve mitochondrial function, reduce inflammation that can contribute to inflammaging, and promote stem cell renewal. (48) Preclinical research indicates that a ketogenic diet can extend longevity and healthspan in mice; whether these results can be extrapolated to humans remains to be seen until clinical trials are conducted. (49) If you are interested in exploring the potential anti-aging benefits of a ketogenic diet, I recommend following a cyclic keto diet, rather than a strict ketogenic diet, over the long term. You can read more about a cyclic ketogenic diet in “A Complete Guide to the Keto Diet.”
How Dietary Protein and Glycine Impact Aging
Dietary protein is a contentious topic in discussions of both overall health and anti-aging and longevity. Several prominent scientists in the field of aging and longevity recommend avoiding or limiting animal protein and keeping overall protein intake low. I don’t agree with these recommendations for several reasons.
First of all, the anti-protein and anti-animal protein sentiment in the aging space originates with a relatively one-dimensional observation, that animal protein increases IGF-1. As I mentioned before, IGF-1 has been inconsistently linked with accelerated aging. (50, 51) However, what some researchers and low-protein diet advocates fail to say is that carbs also increase IGF-1.
Secondly, while amino acids from protein do activate mTOR, this isn’t always a bad thing! We need mTOR activation to build and maintain muscle mass, which is a crucial determinant of healthy aging. (52, 53, 54) However, we don’t want mTOR activated all the time. This is where interventions such as fasting and periodic protein restriction, such as with the FMD, can come in handy because they downregulate mTOR and activate AMPK.
Glycine and Methionine Balance May Be Critical for Healthy Aging
Finally, much of the research on animal protein and longevity has looked at one amino acid found in abundance in animal protein, methionine, in isolation. High-methionine diets are associated with worse health outcomes in aging whereas, in preclinical models, methionine restriction is associated with longevity.
When we take a cue from ancestral diets and balance our methionine intake with adequate glycine, an amino acid found in collagenous cuts of meat and bone broth, we may neutralize the possible detrimental effects of methionine excess on aging. In preclinical research, supplementation with glycine has been found to alleviate adverse changes in gene expression related to aging and extends lifespan to the same degree as methionine restriction. (55, 56) This occurs because glycine is a one-carbon donor that supports the methylation cycle by promoting the formation of the universal methyl donor S-adenosyl methionine (SAMe) and thus playing an intrinsic role in methylation. Glycine also protects against oxidative stress and inflammation, which contribute to aging.
Glycine is also crucial for the synthesis of purines, which are essential components of DNA and necessary for DNA repair. According to research: (57)
“… Glycine supplementation may activate protective cellular pathways that promote longevity when exogenously applied. In contrast, the natural glycine accumulation with age may reflect the organism’s need to upregulate these same cytoprotective pathways to deal with the damage and detrimental changes occurring during aging.”
The key takeaway here is that maintaining methionine and glycine balance in the context of your overall protein intake may be essential for supporting longevity. Eat sufficient protein to support your muscle mass, and make sure to balance your intake of muscle meats with glycine from bone broth, collagenous cuts of meat, and gelatin or collagen peptides. Periodic protein restriction via an FMD or Dr. Joseph Mercola’s KetoFast diet once per month or every few months is also a smart idea.
Other Compounds that Support Healthy Aging: Carnosine and NAD Precursors
Carnosine is a dipeptide molecule found in meats and concentrated in the brain, heart, and muscles of your own body. Emerging research indicates that it is a longevity factor and may slow the aging of human cells. (58) It supports mitochondrial function and inhibits glycation, which ages cells. (59) It also inhibits telomere shortening. (60) Meat is the best dietary source of this compound, though supplements are also available.
NAD is a crucial cofactor for sirtuin enzymes and thus plays an intrinsic role in healthy aging. NAD levels naturally decline with age, and several researchers, most notably David Sinclair from Harvard, are investigating the effects of supplementation with NAD precursor molecules, or molecules that can be transformed into NAD inside the body, on the aging process.
Nicotinamide mononucleotide (NMN) shows particular promise as an NAD-boosting molecule. Unlike NAD, NMN boosts intracellular NAD levels when taken orally. (61) It can be directly transported into cells via the Slc12a8 transporter. (62) Nicotinamide riboside (NR) is another NAD precursor that has been more extensively studied and is a common ingredient in anti-aging nutraceutical supplements. Preclinical research indicates that NAD precursors attenuate age-related DNA damage, improve mitochondrial function, improve cognitive function in aged mice, and “rescue” female fertility during the reproductive aging process. (63, 64, 65)
Nutraceuticals that May Help Slow Aging
Finally, specific nutraceutical compounds may also be useful for slowing the aging process and promoting longevity.
STACs such as quercetin (66), pterostilbene (67), and resveratrol (68) improve sirtuin function by lowering the Km (Michaelis constant) value for sirtuin enzymes; this means STACs reduce the threshold at which sirtuins can be activated, thereby leading to higher sirtuin activity. Natural STACs derived from foods may thus benefit downstream age-related dysfunctions.
Resveratrol is a phytochemical found in red wine, grapes, and blueberries. However, based on the available research, one would need to eat copious amounts of these foods to achieve health benefits, so supplementation may be warranted. Resveratrol appears to slow aging by mimicking calorie restriction and activating xenohormesis, a biological principle by which the consumption of small amounts of toxins (in this case, resveratrol would be considered a mild “toxin”) activates beneficial biological pathways that increase the overall resilience and health of the organism. (69)
Berberine is an alkaloid compound found in the roots of Berberis species, such as goldenseal and Oregon grape root. It is an AMPK activator that acts like metformin, an anti-diabetes drug that has received a lot of attention for its potential longevity-enhancing effects. (70)
Curcumin, mentioned earlier in the anti-aging foods section, can also be taken as a nutraceutical supplement. It aids with the removal of senescent cells, induces the differentiation of stem cells that replenish bone and cartilage tissue, and induces AMPK and sirtuin activity. (71, 72)
Sulforaphane, also mentioned above in the anti-aging foods section, is a sulfur-based phytonutrient created when its precursor molecule, glucoraphanin (found in cruciferous vegetables), is hydrolyzed by the enzyme myrosinase upon chopping or chewing of the vegetables.
Sulforaphane promotes the proliferation and differentiation of neural stem cells, potentially offering protective effects against age-related brain diseases such as Alzheimer’s disease. (73) It also activates the AMPK pathway to attenuate type 2 diabetes-related damage and induces antioxidant pathways that protect against age-related oxidative stress. (74, 75)
Contrary to what we’ve been led to believe for years, age-related declines in health are far from inevitable. Nutrition is a powerful tool for modulating the factors that contribute to aging, and can help us stay healthy, vibrant, and youthful no matter our age!
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