Itโs safe to say we all want to live healthier for longer, but how do we accomplish that goal? Knowledge is power in our search for longevity โ specifically, a deeper understanding of the processes that influence aging. In our Longevity Primer series, weโre diving into various longevity topics to provide a comprehensive overview of ways to increase health span and lifespan. In this second part of the three-part series, weโll build on our introduction to longevity concepts from article one, exploring the science behind longevity, and ultimately the mechanisms that hold the keys to a vibrant and extended life.
This article is part two of a three-part series on the longevity.
- Introduction to Longevity: Understanding the Basics
- Unlocking the Secrets to a Longer, Healthier Life
- Unlocking Longevity: A Holistic Guide to Healthy Aging Through Lifestyle, Nutrition & Supplementation
Contents
- What Are the Major Aging Pathways?
- Growth Pathways and Nutrient Sensing
- Resilience to Molecular Damage and Stress
- Repair and Recycling
- Rejuvenation of Cells, Tissues, and Stem Cells
- Metabolic Health
- Key Takeaways on Core Longevity Concepts
What Are the Major Aging Pathways?
To comprehend longevity, we must first dissect the major aging pathways that dictate how our bodies evolve. These pathways are intricate systems, and various factors can influence their health, including our lifestyle choices. Below, weโve outlined the major aging pathways contributing to longevity, for better or worse.
Growth Pathways and Nutrient Sensing
FoxO
Your body is a well-tuned machine that reacts to signals it receives. Special agents called FoxO transcription factors direct genes to help repair cells and resist stress โ crucial for living longer. There are various ways to activate these factors and initiate the process of cellular autophagy, a healthy โcleaning outโ process of damaged cells.
Among the most effective and efficient methods is to deprive cells of nutrients, influencing our pancreasโ levels of insulin and insulin-like growth factor (IGF-1). By adjusting our diet, incorporating fasting, and using specific supplements, we can suppress insulin and IGF-1 secretion and thus trigger autophagy.
mTOR
Now, letโs talk about mTOR, another pathway linked to how our body senses nutrients. While putting the brakes on mTOR appears effective for extending life and boosting the immune system, we need to be cautious. Too much suppression might harm our immunity and muscle mass.
Safe methods to reduce mTOR signaling may include adopting low-to-moderate protein diets, particularly those low in animal-derived branched-chain amino acids (BCAAs), and incorporating supplements like NOVOS Core, which contains ingredients that have demonstrated moderate mTOR inhibitory effects.
H2S and ATF4
Hydrogen sulfide (H2S), naturally occurring at low levels in the body, offers significant benefits, despite its unpleasant rotten egg odor and potential toxicity when present in high concentrations. In long-lived mice under caloric restriction, H2S is elevated, suppressing IGF-1 and enhancing Nrf2 signaling. The longevity protein ATF4, elevated in slow-aging mice, likely drives increased H2S production.
Boost your H2S levels by incorporating garlic, broccoli, and sprouts into your diet. The active compounds allicin in garlic and sulforaphane in broccoli and sprouts may safely elevate hydrogen sulfide in humans.
AMPK
By monitoring the ratio of AMP to ATP, AMPK (also called AMP-activated protein kinase) is a guardian of cellular energy for longevity and health. It enables cells to adapt under low nutrient or energy conditions induced by exercise and caloric restriction. AMPK activation promotes autophagy and new mitochondria creation, inhibits mTOR, and reduces fatty acids, cholesterol, and proteins, with potential anti-aging benefits.
Pterostilbene, ginger, and l-theanine, all found in NOVOS Core, have been found to increase AMPK levels. Read our Growth Pathways and Nutrient Sensing article for deeper insights on this aspect of longevity and study references.
Resilience to Molecular Damage and Stress
FXR
Bile acid signaling is an intriguing longevity pathway in long-lived mice. The Farnesoid X receptor (FXR) activated by bile acids promotes the expression of detoxification enzymes. While targeting this pathway hasn’t definitively extended mouse lifespan, it may hold relevance for health span and cancer resistance.
HSF1
The body’s heat shock response (HSR), guided by HSF1, could help prevent clumping associated with aging and neurodegenerative diseases. Yet, more research is required to fully understand the advantages of encouraging heat shock proteins (HSPs), as some cancers may hijack this response. Safer, natural methods to increase heat shock proteins include regular exercise, using saunas, and incorporating adaptogens like ginger and rhodiola rosea extracts, found in NOVOS Core.
Hormesis and Mitohormesis
Cells adapt to stress through hormesis, a beneficial response seen in exercise or mild oxidative stress. Mitohormesis operates on the mitochondrial level, triggering protective genes and mitochondrial heat shock proteins. Elevated ATF4, a key protein in cellular responses to stress, in long-lived mice, and increased FGF21, a hormone involved in regulating metabolism and energy balance, with exercise or low-protein diets demonstrate the potential benefits. NOVOS Core includes glucosamine and pterostilbene, which are believed to act through hormesis or mitohormesis.
Nrf2
Nrf2, a vital controller of longevity and cancer defense, boosts genes for stress resistance. Long-lived animals exhibit increased Nrf2 levels, underscoring its significance. Sulforaphane, found in broccoli and sprouts, activates Nrf2, extending lifespan. With pterostilbene and salidrosides from rhodiola, NOVOS Core encourages brief stress and hormesis, activating Nrf2 for better health.
Iron Levels, Aging, and Cancer Risk
Iron, known for promoting oxidative stress and causing damage to proteins and DNA, may pose risks, particularly in aging. Research indicates that reducing iron levels could offer protection against cancer. Understanding these pathways of molecular damage and stress unveils potential interventions for enhancing resilience and overall well-being.
Read our article Resilience to Molecular Damage and Stress for more information about our bodiesโ mechanisms to combat molecular damage and stress.
Repair and Recycling
Sirtuins and NAD
Humans have seven sirtuin proteins, primarily acting as deacetylases to modulate protein function. Although SIRT1, once thought to extend lifespan with resveratrol, raised doubts, SIRT6 has proven promising. Research underscores SIRT6’s ability to extend mouse lifespan, surpassing the effects of SIRT1 and trendy but poor-performing longevity ingredients like resveratrol. NOVOS Core contains pterostilbene, a promising ingredient that positively impacts sirtuins.
NAD supplementation enhances healthspan in mice, and NOVOS Boost, with NMN, raises NAD+ levels in humans.
Autophagy: Self-Eating for Cellular Renewal
Autophagy, the cellular self-eating process, plays a pivotal role in degrading internal structures. Mice overexpressing the autophagy gene Atg5 demonstrate extended lifespan, showcasing its benefits. Various pathways stimulate autophagy, including TFEB, mTOR inhibition, ATF4, AMPK activation, fasting, and pterostilbene in NOVOS Core.
DNA Repair
DNA, the blueprint of life, faces threats with aging, leading to protein function impairment or the formation of harmful cells. Enhanced DNA repair involving SIRT6, PARP, and other proteins improves longevity. Minimizing carcinogenic exposure, adopting a diet high in plants, and consuming specific supplements aid DNA repair.
TFEB and Aging
TFEB, a transcription factor, manages lysosomal biogenesis, autophagy, and protein recycling amid nutrient scarcity. Longevity pathways such as mTOR suppression, AMPK, GSK3, and Akt converge on TFEB. TFEB activation, which decreases with age, impacts autophagy and antibody production. NOVOS Core includes TFEB-activating compounds like pterostilbene and fisetin.
Read our article on Repair and Recycling for in-depth information on cellular repair and recycling pathways.
Rejuvenation of Cells, Tissues, and Stem Cells
Epigenetic Reprogramming: Renewing Cellular Youth
Our body’s gene instructions are influenced by epigenetic marks, which change as we age. Scientists have explored a process similar to rejuvenation in children, called cellular reprogramming. In mice, specific factors (Yamanaka factors) briefly activated reversed DNA aging signs, suggesting a potential for rejuvenation. While safe reprogramming for consumers is not yet available, NOVOS Core supports maintaining a youthful epigenome with ingredients like microdosed lithium, glycine, alpha-ketoglutarate, ginger, and pterostilbene.
Activating PGC-1ฮฑ: Exercise, Mitochondria, and Aging
PGC-1ฮฑ, crucial for mitochondrial biogenesis, plays a role in aging-related mitochondrial dysfunction. Caloric restriction, exercise, and compounds like pterostilbene in NOVOS Core activate PGC-1ฮฑ, potentially benefiting lifespan and health span.
Telomerase, Longevity, and Cancer Prevention
Telomerase, safeguarding chromosome ends (telomeres), extends lifespan in mice. NOVOS Core ingredients like microdosed lithium, magnesium, and pterostilbene support telomere maintenance.
Aging and Cell Death: Balancing Apoptosis and Senescence
Metabolically stressed cells face the choice of apoptosis or senescence. Excessive cell death or resistance to apoptosis contributes to age-related diseases. NOVOS Core, shown to counter senescent cells in an independent study, offers a potential solution.
Read our article Rejuvenation of Cells, Tissues, and Stem Cells for deeper insights into the science of cellular and tissue rejuvenation amid molecular damage.
Metabolic Health
LDL Cholesterol and ApoE
LDL cholesterol and ApoE, a cholesterol carrier, significantly affect how long and healthy we live. Lowering LDL cholesterol might help prevent heart problems, and studies suggest that having lower LDL is linked to a longer life. ApoE genes, which come in three types (E2, E3, E4), may hold clues to longevity: If you have the E4 type, there’s a higher chance of Alzheimer’s and a shorter life, while E2 is protective. Making healthy choices like managing lipids, exercising, and eating omega-3-rich foods might help counter the effects of ApoE4.
Parabiosis
In a parabiosis study, researchers found potential rejuvenation possibilities when linking the blood of a young mouse to an old one. One popular explanation for these benefits is the potential dilution of harmful factors in the old mouseโs blood.
Adipokines and Myokines
Adipokines are substances released by fat tissue, with leptin and adiponectin being the most well-known. Adiponectin, produced by healthy fat tissue, enhances insulin sensitivity. Human weight loss and extended lifespan in mice due to growth hormone deficiency elevate adiponectin levels.
Similarly, myokines are substances secreted by muscles. Two notable myokines are FGF21 and brain-derived neurotrophic factor (BDNF). BDNF declines with age, but restoring it through gene therapy extends the health span of mice. Exercise, especially resistance training like weight lifting, and intermittent fasting stimulate myokine release in animal models.
Cortisolโs Effects on Muscle, Skin, and Heart Health
Cortisol, a hormone linked to stress, can lead to muscle loss and skin issues in excessive amounts. However, not all stress is harmful; mild or short-term stress, known as eustress, can be beneficial through the hormesis process (discussed above).
Surprisingly, slightly increased cortisol levels occur during caloric restriction in mice and temporarily during fasting in humans. Vitamin C, present in NOVOS Core, can regulate the cortisol-related stress response.
Insulin Sensitivity
When we eat carbohydrates and sugars, the pancreas releases insulin to help cells utilize the sudden sugar influx. This process of handling high sugar with low insulin is insulin sensitivity. While proper insulin secretion is crucial to prevent tissue damage from excess blood sugar, a factor in aging, its role in lifespan extension might be less significant than we initially thought.
Inflammation
Acute inflammation, marked by redness, swelling, and pain, is the body’s response to infection and tissue damage. Less apparent is sterile inflammation, a low-level state that increases with age, often termed “inflammaging.” Blood tests measure inflammation using markers like CRP, TNFa, and IL-6, linked to age-related diseases.
Recent research highlights senescent cells as a major contributor to inflammation. In human studies, anti-aging compounds like rapamycin or fisetin, included in NOVOS Core, have effectively reduced senescent cells.
Read our article on Metabolic Health for more information on this essential pillar of longevity.
Key Takeaways on Core Longevity Concepts
In our discussion of longevity, weโve explored essential concepts and mechanisms that influence the aging process. Understanding the significance of factors like DNA repair, autophagy, and metabolic health provides insights into how we can enhance our lifespan and health span.
Longevity is about more than just nutrition; it involves a mix of diet, exercise, and the right supplements to help our bodies function better. Improving how our cells handle stress and repair themselves is crucial. Keeping our metabolism healthy and reducing inflammation also play key roles. Techniques that help rejuvenate cells and tissues can make a significant difference in promoting a longer and healthier life.
Looking ahead, our final article in this Longevity Primer series looks at practical lifestyle approaches. We’ll provide insights and tips to incorporate longevity-promoting habits into your daily routine.
