In pursuit of the age-old question, "How can we live longer and healthier lives?" humanity has explored various paths, from ancient shamanic rituals to modern cryopreservation, all while hoping future advances might solve the challenges of unfreezing.

Amid these eclectic methods, the quest for longevity remains a cornerstone of medical progress. Scientists are diligently unraveling the molecular intricacies of aging and ways to mitigate its effects. Thanks to these scientific advances, we now have access to select longevity supplements that offer tangible benefits.

With public interest surging and investments booming, the market for dietary supplements has expanded dramatically. Amidst this proliferation, it's essential to discern which supplements genuinely enhance longevity and which are less effective.

This article explores the top supplements that have been scientifically validated to slow aging, enhance cellular health, and contribute to overall well-being. We'll exclusively focus on supplements backed by rigorous research, providing you with the knowledge to make well-informed decisions about incorporating them into your routine.

The Role of Supplements in Supporting Longevity

Longevity is not just about living longer but about living better. Smart supplementation can play a significant role in promoting healthy aging.

As we age, our bodies wear down. That manifests in decreased physical and cognitive abilities, increased susceptibility to disease, and overall poor health. From wrinkles and loss of skin elasticity to decreased energy levels and memory lapses, the symptoms of aging can be disheartening. That's why it's crucial to explore not only how to live longer but also how to remain healthy with a good quality of life into older age.

Supplements play a critical role in maintaining longevity and alleviating the symptoms associated with aging. Unlike standard vitamins and dietary supplements, which simply target nutrient deficiencies, longevity supplements go one step further to target and intervene in the biological processes underlying aging. These specialized supplements act at the cellular level to counteract the 12 hallmarks of aging, including oxidative stress, DNA damage, and others.

Incorporating scientifically validated longevity supplements into your daily regimen can yield numerous advantages, including:

• Enhanced Cellular Function and Energy Production: These supplements support the vitality of your cells, tissues, and organs by optimizing cellular function and energy production.
• DNA Repair: Some supplements facilitate the repair of damaged DNA, an accumulation of which can speed up the aging process.
• Reduction of Inflammation and Oxidative Stress: These supplements help mitigate inflammation and oxidative stress, both of which are linked to chronic diseases and aging.
• Activation of Longevity Pathways: Longevity supplements influence molecular pathways known to extend lifespan, offering a foundation for healthier aging.
• Slowing Age-Related Diseases: Regular intake of these supplements may slow the progression of various age-related conditions.
• Safety and Tolerance: These supplements are generally safe and well-tolerated by humans, making them a practical addition to daily health routines.
• Lifespan Extension: Evidence from laboratory studies on model organisms has demonstrated the potential of these supplements to extend lifespan.

The Scientific Basis Behind Longevity Supplements

Longevity supplements that truly work have been supported with evidence by numerous studies on model organisms, cell cultures, and even clinical trials. Here's an overview of their mechanisms of action:

• Energy metabolism declines with aging, but supplements can protect mitochondria, the organelles that produce energy, from the harmful effects of oxidative stress (1). They can also restore decreased levels of NAD+, a cofactor for many molecular processes, including metabolic function (2).

• FOXO3 is a gene, a transcriptional factor, and a crucial regulator of cell function and longevity. Some supplements can activate its expression, thereby boosting mechanisms of telomere protection, increasing telomerase activity, and modulating inflammatory cytokine levels. This showcases their anti-aging effects and potential for promoting longevity (3).

• Longevity supplements can activate sirtuins, a family of proteins that help maintain the epigenome and play an important role in keeping cells healthy and increasing longevity. These proteins have been dubbed "longevity genes" for their significant impact on aging and health. (4). 

• AMPK activation, either directly or via indirect activators like supplements and exercise, can delay aging and extend lifespan (5). 

• Inhibition of mTOR complex 1 that is a central regulator of mammalian metabolism and physiology, whose dysregulation can lead to diabetes, obesity, depression, and certain cancers (5).

• ROS/RNS are byproducts of normal cellular metabolism, particularly in the mitochondria during energy (ATP) production. When produced in excess, they can cause oxidative stress that leads to damaged cellular components, such as DNA, proteins, and lipids. Supplements can both combat oxidative stress and activate the internal antioxidative system (6).

• Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and  interleukin-11 (IL-11) are central to the development and maintenance of inflammation. When inflammation becomes chronic, it can damage tissues and organs, induce premature senescence, and be a significant factor in the development of various age-related diseases. Some supplements can decrease the levels of pro-inflammatory cytokines, thereby reducing chronic inflammation (7).

• Autophagy is a vital cellular process by which cells break down and recycle damaged components, maintaining cellular health and function, and controlling the number of senescent cells. This self-cleansing mechanism helps remove dysfunctional proteins and organelles, preventing their accumulation, which is associated with age-related diseases. By enhancing autophagy, cells can better resist stress, maintain homeostasis and inhibit mTOR signaling pathway, promoting longevity. Research shows that fasting and certain supplements can stimulate autophagy, further supporting healthy aging and longevity (8).

What Are The Best Supplements for Longevity?

The best longevity supplements, also known as longevity molecules, are those that have been shown to target and ameliorate the aging process. Let's explore the criteria for choosing such supplements in more detail.

• Choose formulas backed by strong scientific evidence to support their potential to prolong healthy life and reduce age-related changes.

• Supplements should be orally bioavailable, i.e. easily digested and utilized by the body to exert its beneficial effects. 

• The supplement should have a well-established safety profile, with minimal risk of side effects when taken as recommended.

• Ideally, a supplement should affect multiple pathways involved in the aging process, providing a wide range of benefits for longevity.

• The correct dosage, formulation, and regimen are crucial. Supplements should contain clinically effective doses of active ingredients. Too little may be ineffective, while too much can lead to side effects. The formulation should ensure optimal delivery and absorption of these ingredients into the body.

Specialized Supplements for Aging

Below is a list of scientifically-backed supplements considered to support healthy aging and longevity:

Longevity:

• Calcium Alpha-Ketoglutarate: An intermediate of the Krebs cycle (9). This compound helps restore blood calcium levels, supports numerous bodily functions including muscle formation and wound healing, attends to energy production and nutrient metabolism, reduces chronic inflammation, supports cellular health, and helps remove senescent cells.

• Astragalus Root Extract: Known in Chinese medicine (10), it stimulates telomerase activity, enhances immune responses, maintains a healthy balance of gut microbiota preventing the overgrowth of harmful bacteria, and affects DAF-15/FOXO transcription factors.

• Chondroitin Sulfate: An important structural component of cartilage (11). It provides the necessary components for the body to produce new cartilage, contributes to overall joint health and function, and reduces inflammation.

• Berberine: A powerful plant-derived alkaloid (12). It reduces blood sugar levels preventing the development of glucose spikes, improves insulin sensitivity, promotes glucose metabolism, suppresses NF-κB diminishing inflammation and oxidative stress, activates AMPK, and enhances the function of Sirt1, boosting autophagy.

• Creatine: A naturally-occurring compound found in meat and fish, and produced in the human body (13). It enhances muscle mass and strength, supports sustained muscle energy production, assists in ATP regeneration, and aids in cognitive function, preventing the development of neurodegenerative disorders.

• Taurine: A chemical known as an amino sulfonic acid (14). It supports the body's natural melatonin production, decreases DNA damage, regulates crucial antioxidant enzymes, assists in detoxification and preventing fatty liver disease, helps regulate calcium levels in muscles ensuring efficient muscle performance and may help prevent cramping, reduces physiological symptoms of stress and anxiety, acting as a neuromodulator, influencing inhibitory neurotransmission in the brain.

• Glycine: The smallest amino acid (15). It mitigates oxidative stress during sleep and in safeguarding cellular health, plays a pivotal role in the synthesis of creatine, stimulates autophagy, supports muscle maintenance and repair, acts in collagen production, and regulates the critical sleep-wake cycle, decreases lipid peroxidation.

• Spermidine: A natural polyamine (27). It induces autophagy by activating the AMPK pathway and inhibiting the mTOR pathway, slows down epigenetic alterations, promotes cellular renewal, aids in reducing telomere erosion, maintains gut microbiome balance and intestinal health, and plays a pivotal role in mitochondrial quality control through mitophagy.

• Olive Leaf Polyphenols (like Oleuropein found in extra virgin olive oil) (28). They activate the AMPK pathway leading to the induction of autophagy, modulate the sirtuin pathway particularly SIRT1, enhance blood flow to the brain, support overnight wound healing and reduce skin inflammation, enhance mitochondrial respiration and energy metabolism, boost cognition and memory protecting against cognitive decline.

• Apigenin: Belongs to the flavone class (29). It protects the skin from oxidative stress, reduces inflammation, inhibits the activity of enzymes involved in skin aging, promotes collagen synthesis, modulates the activity of enzymes involved in NAD+ metabolism, activates SIRT1, modulates cellular senescence and autophagy.

• Omega-3 Fatty Acids: Polyunsaturated fats, or "healthy fats" (16). They maintain heart health, support cognitive function, and provide inflammation control.

Essential Vitamins for Longevity:

• Vitamin D: A fat-soluble vitamin (17). It has a positive effect on bone health, supports immune function, improves protein homeostasis, and reduces the development of age-related diseases.

• Vitamin E: A fat-soluble vitamin (18). It has strong antioxidant properties, supports skin health, and boosts mechanisms that protect from cellular aging.

• Vitamin C: A water-soluble vitamin (19). It supports cardiovascular health and bone density, battles against oxidative damage, prevents premature senescence, and enhances immune function.

• B3 Vitamin Family: Niacin, Nicotinamide Mononucleotide, and Nicotinamide Riboside (20). These boost NAD+ levels, which decline with age, support cellular metabolism and DNA repair, support heart health by lowering cholesterol, and maintain brain health by generating key brain chemicals.

Key Minerals and Antioxidants:

• Zinc: An essential mineral for immune function (21). It plays a critical role in DNA synthesis and repair, improves sleep quality, supports immune health, improves gut microbial composition, and maintains the integrity of the intestinal barrier.

• Magnesium: A vital mineral that aids sleep regulation (22). It acts as a cofactor for various repair enzymes, facilitates biochemical reactions for repairing damaged DNA, promoting genomic stability, aids neurotransmitter regulation and nerve signal transmission, contributes to enzyme function across carbohydrate, fat, and protein metabolism, aids in insulin regulation and balanced blood sugar levels, maintains a healthy inflammatory response, is crucial for ATP synthesis, and contributes to stress reduction and tension relief.

• Astaxanthin: A natural carotenoid pigment (23). It combats oxidative damage at a cellular level, reduces DNA damage, acts as a guardian for mitochondria, influences proteins such as Nrf2, Sirt1, and Klotho associated with longevity, modulates FOXO3 gene expression, promotes cardiovascular health, reduces inflammation, and mitigates oxidative stress in blood vessels, and shields skin against UV light damage reducing wrinkles and improving skin elasticity.

• Pterostilbene: A stilbenoid found in blueberries and grapes (24). It activates sirtuins, protects the skin from damage caused by free radicals, modulates molecular pathways implicated in inflammation and oxidative stress, and helps regulate blood sugar levels by preventing glucose spikes.

• Quercetin: A flavonoid with potent antioxidant properties (25). It activates the AMPK/mTOR pathway, SIRT1 pathway, and the extracellular signal-regulated kinase (ERK) pathway, scavenges free radicals thereby mitigating oxidative stress, protects the skin from the effects of photoaging, exhibits anti-inflammatory properties helping to alleviate chronic inflammation, maintains the integrity of the gut barrier, stimulates autophagy and enhances cellular clearance.

• Fisetin: A flavonoid polyphenol (26). It neutralizes harmful free radicals and reduces oxidative stress, mimics caloric restriction thereby inducing autophagy, targets and removes "zombie" cells, inhibits inflammation, and reduces markers of cellular aging in various tissues.

Longevity Supplements Myths and Marketing Gimmicks 

Navigating the often complex and crowded world of supplements can be daunting, but we're here to help. In this section, we'll debunk common myths, unmask marketing ploys, and provide you with research-backed insights to help you make informed decisions about your health.

1. Can a single "miracle pill" drastically slow down aging? 

No. Aging is a complex, multifactorial process that cannot be addressed by a single supplement. Therefore, supplement protocols as part of a portfolio approach for longevity are the best way to take into account the complexity of aging, especially when combining them with specific lifestyle modifications that have been shown to slow or reverse damage. 

2. Marketing often relies on bold claims and anecdotal testimonials. Are their statements like "reverses aging" or "guarantees 20 extra years'' supported by rigorous scientific evidence? Generally, it’s just catchy titles rather than realistic data.

3. Terms like "clinically proven" or "doctor recommended" can be misleading. Verify claims by checking if the product or ingredient has been independently reviewed and published in reputable scientific journals.

4. The belief that "natural" automatically means safe and effective is a common misconception. First and foremost, the ingredients must be of high purity, in the correct dosage, and work synergistically, rather than merely being "eco-friendly”.

How to Choose the Right Longevity Supplements for You

Here’s a comprehensive guide to help you navigate how to choose the right longevity supplements:

Choose high-quality supplements

• Check third-party testing,
• Revise company reputation,
• Analyze the scientific transparency of ingredients.

Choose a supplementation plan that fits your goals

• Define your individual health needs,
• Don’t forget to consult with a healthcare provider.

Chose supplements that are easy to integrate into a healthy lifestyle

• Add it to your balanced diet,
• Choose supplements that support your regular exercise,
• Aid in your stress management,
• Be consistent and monitor your wellness.

Create a supplement protocol

• Choose supplements that complement and enhance each other's effectiveness,
• Determine the timing of supplementation to prevent supplements from interfering with each other,
• Establish a time frame for your protocol that will maximize its benefits.

Jung’s Total Longevity System™: Why We Made This

At Jung+, we understand that achieving optimal health and longevity requires more than a one-size-fits-all approach. That's why we've created the Total Longevity System™—a comprehensive 360-degree program that helps you take control of aging.

Our goal is to promote longevity for the billions, not just billionaires.

We have developed a program that blends seamlessly with your lifestyle and behavioral modifications for maximum effect. Whether you need support for your sleep, intermittent fasting, or an overall longevity-focused complex, you'll find it at Jung+.

By integrating science-based supplements with personalized lifestyle recommendations, we ensure that every element of your daily routine works synergistically to promote longevity. Whether it's boosting autophagy, reducing inflammation, or increasing energy levels, you'll find what you need in our holistic approach to a longer, healthier, and more energized life.

References:

1. NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease (2023). Journal of Biological Chemistry.
2. Dietary supplementation with NAD+-boosting compounds in humans: Current knowledge and future directions (2023). The Journals of Gerontology: Series A.
3. Astaxanthin as a Putative Geroprotector: Molecular Basis and Focus on Brain Aging (2020). Marine Drugs.
4. The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling (2013). Cell.
5. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states (2006). Diabetes.
6. Astaxanthin: A potential mitochondrial-targeted antioxidant treatment in diseases and with aging (2019). Oxidative Medicine and Cellular Longevity. 
7. Zinc is an Antioxidant and Anti-Inflammatory Agent: Its Role in Human Health (2014). Frontiers in Nutrition. 
8. The effect of fasting or calorie restriction on autophagy induction: a review of the literature (2018). Ageing Research Reviews. 
9. Alpha-Ketoglutarate dietary supplementation to improve health in humans (2022). Trends in Endocrinology & Metabolism. 
10. Inhibition of polyglutamine-mediated proteotoxicity by Astragalus membranaceus polysaccharide through the DAF-16/FOXO transcription factor in Caenorhabditis elegans (2012). Biochemical Journal. 
11. Anti-inflammatory and anti-aging effects of chondroitin sulfate (2020). Neurology, Neuropsychiatry, Psychosomatics. 
12. Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis (2012). Biochimica et Biophysica Acta.
13. Creatine improves health and survival of mice (2008). Neurobiological Aging.
14. Taurine deficiency as a driver of aging (2023). Science. 
15. Glycine and aging: Evidence and mechanisms (2023). Ageing Research Reviews. 
16. Omega 3-metabolism, absorption, bioavailability and health benefits–A review (2019). PharmaNutrition.
17. Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes SKN-1, IRE-1, and XBP-1 (2017). Cell Reports.
18. Vitamin E in human skin: organ-specific physiology and considerations for its use in dermatology (2007). Molecular Aspects of Medicine. 
19. Aging and its treatment with vitamin C: a comprehensive mechanistic review (2021). Molecular Biology Reports.
20. Therapeutic potential of NAD-boosting molecules: the in vivo evidence (2015). Cell Metabolism.
21. Zinc, aging, and immunosenescence: an overview (2015). Pathobiology of aging & age related diseases. 
22. Magnesium Role in Health and Longevity (2018). Trace Elements and Minerals in Health and Longevity. 
23. Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential (2011). Alternative Medicine Review.
24. Effect of resveratrol and pterostilbene on aging and longevity (2018). Biofactors.
25. Benefits of Quercetin in Age-Related Diseases (2022). Molecules.
26. Fisetin is a senotherapeutic that extends health and lifespan (2018). EBioMedicine.
27. Induction of autophagy by spermidine promotes longevity (2009). Nature Cell Biology.
28. Bioactive Compounds and Quality of Extra Virgin Olive Oil (2020). Foods.
29. The Therapeutic Potential of Apigenin (2019). International Journal of Molecular Sciences.