Sarah SmithFor the uninitiated, aging involves several biological mechanisms collectively known as the hallmarks of aging. These mechanisms are known to drive the aging process and contribute to age-related diseases. By targeting these hallmarks, nutraceuticals broadly aim to enhance healthspan and longevity. Unfortunately, this isn’t the entire story.
Notable longevity expert, Matt Kaeberlein, attributes the hallmarks to researching “under the lamp post”. By that, he means that we are not going to understand more about biology by only focusing on topics we already attribute to aging. The hallmarks were update recently to include an “unknown” category, and a new hallmark, called CHIP, was recent proposed. We’re simply not done discovering the root causes of aging. When you look at the hallmarks themselves, you can see that there is a large portion of biological overlap, and this biological cross-talk makes their combined study all the more important.
In fact, that is the exact point of this post. We are going to explore the top 10 combination nutraceuticals for 2024 that focus on multiple hallmarks of aging. As an added bonus, they are hierarchically ordered by their likelihood of true longevity effects in the average American. By that I mean those of us that — like myself — do not exercise vigorously and those that eat a moderately poor diet. Before jumping into the pills, the list below outlines the hallmarks that the nutraceuticals will cover, but keep in mind that not all supplements cover all the hallmarks listed below.
Hallmarks of Aging
Genomic Instability
Genomic instability refers to the accumulation of DNA damage over time, leading to cell malfunction and disease. This instability causes DNA mutations happen more frequently, feeding forward more genomic instability.
Telomere Attrition
Telomeres are protective caps at the ends of chromosomes that shorten with each cell division. Telomere attrition leads to cellular aging, senescence (see below), and eventual cell death, and the length of telomeres is sometimes used as a clinical biomarker of aging. To be fair, this metric varies widely by cell type, tissue type, and can rapidly change with environment.
Epigenetic Alterations
Epigenetic changes involve modifications in gene expression without altering the DNA sequence. Changes can be thought of as gluing blocks (methylation) to a train track (gene). The train track stays the same, but the train (polymerase) cannot pass through the block (reduced/inhibited gene expression). These changes can disrupt normal cellular function and are widely used to compare chronological age to the true biological age.
Loss of Proteostasis
Proteostasis involves maintaining the balance and proper function of proteins within cells. The speed of protein formation and the organization of the protein folds determines the eventual functionality. If cells fail to meet both requirements, protein misfolding can occur. Aging disrupts this balance, leading to protein aggregation and cellular dysfunction.
Deregulated Nutrient Sensing
Nutrient sensing pathways, such as insulin signaling, regulate metabolism and energy balance. Their goal is to take in the proper substances and in the proper proportion. Dysregulation of these pathways can accelerate aging and promote age-related diseases.
Mitochondrial Dysfunction
Mitochondria are the proverbial “powerhouses” of cells, providing energy and so much more. Broadly, dysfunction in mitochondria leads to a reduction in cellular energy and increased oxidative stress, contributing to many other hallmarks of aging.
Cellular Senescence
Cellular senescence occurs when cells fail to get a passing grade during one of the cell cycle checkpoints that determines things like damage. This causes a stop to cellular division and can shift the phenotype to a more proinflammatory state. These cells avoid regular immune clearance mechanisms, causing their accumulation, and resulting in the secretion of harmful inflammatory factors. This process promotes aging and various age-related diseases.
Stem Cell Exhaustion
Stem cells are essential for tissue regeneration and repair. Over time, DNA damage, epigenetic alterations, and changes to the stem cell niche cause a functional decline. Without stem cell’s ability to function properly, tissue degeneration and aging occur more rapidly.
Top 10 Combination Supplements
1. RESTORIN by Seragon Biosciences
RESTORIN combines NAD+ precursors, rapamycin, senolytics, and sirtuin-activating compounds (STACs). This powerful combination targets genomic instability, cellular senescence, and mitochondrial dysfunction. Rapamycin, specifically, inhibits the mTOR pathway, enhancing autophagy and reducing the secretion of inflammatory cytokines associated with the senescence-associated secretory phenotype (SASP). RESTORIN enhances cellular energy, promotes DNA repair, and reduces inflammation, making it one of the most comprehensive anti-aging supplements available.
2. Elysium Basis
Elysium Basis features nicotinamide riboside (NR) and pterostilbene, which target genomic instability and mitochondrial dysfunction. This combination supports cellular health by boosting NAD+ levels and enhancing sirtuin activity, crucial for maintaining cellular function and longevity.
3. Tru Niagen (Nicotinamide Riboside)
Tru Niagen focuses on boosting NAD+ levels to combat genomic instability and mitochondrial dysfunction. By increasing NAD+, it supports cellular energy production and DNA repair, essential for healthy aging.
4. NOVOS Core
NOVOS Core includes trehalose, acetic acid, nattokinase, rutin, lutein, zeaxanthin, and inulin. This diverse blend targets multiple aging pathways, including genomic instability, loss of proteostasis, and cellular senescence. NOVOS Core promotes cellular health, metabolism, and cardiovascular function.
5. Qualia Life
Qualia Life combines CoQ10, PQQ, NADH, alpha-lipoic acid, and acetyl-L-carnitine to target mitochondrial dysfunction and deregulated nutrient sensing. This formula enhances mitochondrial health, boosts energy levels, and supports cognitive function.
6. Tally Health
Tally Health‘s blend of calcium alpha-ketoglutarate, quercetin, trans-resveratrol, fisetin, and spermidine addresses cellular senescence, genomic instability, and deregulated nutrient sensing. This combination reduces inflammation, aids cellular repair, and enhances immune function.
7. Neurohacker Collective Eternus
Eternus includes PQQ, CoQ10, alpha-lipoic acid, acetyl-L-carnitine, and resveratrol. It targets mitochondrial dysfunction, epigenetic alterations, and deregulated nutrient sensing, supporting cellular energy, mitochondrial function, and cognitive health.
8. Ageless Cell by Life Extension
Ageless Cell features fisetin, gamma-tocotrienol, quercetin, and pterostilbene, targeting cellular senescence and genomic instability. This supplement reduces cellular senescence and improves overall cellular health and longevity.
9. NAD3 Fountain of Youth
NAD3 combines NAD+ with other compounds to address genomic instability, mitochondrial dysfunction, and epigenetic alterations. It boosts metabolism, repairs damaged cells, and maintains mitochondrial function.
10. Mitopure (Urolithin A)
Mitopure focuses on urolithin A to target mitochondrial dysfunction and loss of proteostasis. It enhances mitophagy, improving mitochondrial function and muscle health, which are critical for longevity.
Conclusion: The Ideal Nutraceutical
Combining the best features of the top nutraceuticals could yield an ideal supplement for longevity. This hypothetical product, “Longevity Master,” would include:
- NAD+ Precursors: Boosting cellular energy and DNA repair.
- Rapamycin: Inhibiting mTOR pathway, enhancing autophagy, and reducing SASP.
- Sirtuin Activators (e.g., Resveratrol, Pterostilbene): Enhancing DNA repair and cellular function.
- Mitochondrial Support (e.g., CoQ10, PQQ): Improving mitochondrial health and energy production.
- Anti-Inflammatory Agents: Reducing chronic inflammation.
- Proteostasis Enhancers (e.g., Trehalose): Maintaining protein balance and cellular health.
- Nootropics/Cognitive Boosters (e.g. Lion’s Mane): Enhancing our cognitive abilities and staving off cognitive decline.
“Longevity Master” would comprehensively target the key hallmarks of aging, offering the best chance of enhancing healthspan and longevity based on current scientific understanding.
By targeting multiple aging mechanisms, these nutraceuticals offer promising interventions to promote healthy aging and extend lifespan. Always consult with a healthcare provider before starting any new supplement regimen.
