THE SCIENCE
Understanding the 12 Hallmarks of Aging
Key Mechanisms Behind Aging Processes
Aging is a complex biological process driven by multiple factors at the molecular and cellular levels. Researchers have identified 12 key hallmarks of aging that contribute to the progressive decline in physiological function. Understanding these hallmarks provides valuable insights into the mechanisms of aging and helps identify potential interventions that promote longevity and health span.
The 12 Hallmarks of Aging, first introduced by López-Otín et al. in 2013* and expanded in 2023, define the core biological processes driving aging across the entire body—not just the skin. These hallmarks affect cellular function, metabolism, immunity, and tissue regeneration, contributing to wrinkles, muscle loss, cognitive decline, and reduced healing capacity.
One major factor is the accumulation of senescent cells, which fuels inflammation and tissue degradation. Understanding these mechanisms has led to targeted interventions like senolytics and regenerative therapies, designed to slow or even reverse aging at the cellular level.
Genomic Instability
Genomic instability refers to the accumulation of DNA damage caused by environmental factors, radiation, and errors in DNA replication.
Increased mutation rates lead to cell dysfunction, contributing to age-related diseases like cancer and neurodegeneration.
Strategies such as DNA repair-enhancing compounds, antioxidants, and lifestyle modifications like reduced exposure to toxins can mitigate genomic instability.
Telomere Attrition
Telomeres are protective caps at the ends of chromosomes that shorten with each cell division.
Shortened telomeres lead to cellular aging (senescence) and reduced tissue regeneration.
Telomerase-activating compounds, such as Cycloastragenol and Astragaloside IV, along with stress management and regular exercise, may help maintain telomere length.
Epigenetic Alterations
Changes in gene expression that occur without altering the DNA sequence, influenced by environmental factors.
Disrupts normal cellular function and contributes to age-related diseases.
Supporting healthy epigenetic regulation through NAD+ boosters like Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN), along with polyphenols such as Resveratrol and Fisetin, may help maintain proper gene expression.
Loss of Proteostasis
The failure of protein quality control systems, leading to misfolded or damaged proteins accumulating in cells.
Causes neurodegenerative diseases like Alzheimer’s and Parkinson’s.
Enhancing proteostasis through heat shock protein activators, autophagy-inducing compounds, and dietary polyphenols may help maintain protein homeostasis.
Deregulated Nutrient Sensing
The body’s ability to detect and respond to nutrient levels declines with age.
Leads to metabolic disorders like diabetes and obesity.
Caloric restriction, intermittent fasting, and modulating nutrient-sensing pathways through NAD+ boosters such as Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN), along with sirtuin-activating compounds like Resveratrol and Fisetin, may support metabolic health.
Mitochondrial Dysfunction
Mitochondria, the energy producers of the cell, lose efficiency with age.
Leads to reduced energy production, oxidative stress, and chronic fatigue.
Supporting mitochondrial health through NAD+ boosters like Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN), along with antioxidants such as Quercetin, and mitochondrial function enhancers like Cycloastragenol and Astragaloside IV, may enhance energy production and reduce oxidative stress.
Cellular Senescence
Senescent cells stop dividing but remain metabolically active, releasing inflammatory factors.
Promotes chronic inflammation and tissue degradation.
Clearing senescent cells through senolytic compounds like Fisetin and Quercetin, along with lifestyle interventions such as fasting and exercise, may reduce inflammation and support tissue health.
Stem Cell Exhaustion
A decline in the regenerative capacity of stem cells, reducing tissue repair and maintenance.
Leads to impaired healing, muscle loss, and immune dysfunction.
Supporting stem cell function through NAD+ boosters like Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN), along with botanical extracts such as Aloe vera, Sea Buckthorn, and Panax Notoginseng, may enhance tissue repair and regeneration.
Altered Intercellular Communication
Disruptions in the signaling between cells, leading to chronic inflammation and immune system decline.
Contributes to autoimmune diseases and increased susceptibility to infections.
Anti-inflammatory diets, regular physical activity, and modulating intercellular communication through NAD+ boosters like Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN), along with anti-inflammatory compounds such as Fisetin, may help reduce inflammation and support immune function.
Disabled Macroautophagy
A decline in the body’s ability to remove damaged cellular components through autophagy.
Leads to accumulation of waste products and increased risk of age-related diseases.
Enhancing autophagy through botanical compounds like Cycloastragenol, Astragaloside IV, and Resveratrol, along with lifestyle interventions such as fasting and ketogenic diets, may promote cellular cleanup processes.
Chronic Inflammation ("Inflammaging")
A persistent low-grade inflammation associated with aging.
Drives multiple age-related diseases, including cardiovascular disease and neurodegeneration.
Adopting an anti-inflammatory diet (e.g., Mediterranean diet), curcumin supplementation, incorporating anti-inflammatory compounds such as Quercetin and Resveratrol, and prioritizing proper sleep may help reduce chronic inflammation.
Dysbiosis (Gut Microbiome Imbalance)
An imbalance in gut bacteria leading to digestive and immune dysfunction.
Weakens immunity, increases inflammation, and affects brain health.
Restoring gut microbiome balance through dietary polyphenols like Resveratrol and Fisetin, along with prebiotics, probiotics, fiber-rich diets, and fermented foods, may improve digestive health and enhance immune function.
* Cell 2013 Jun – The Hallmarks of Aging, Carlos López-Otín, Maria A. Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer
** Cell 2023 Jan – Hallmarks of aging: An expanding universe, Carlos López-Otín, Maria A. Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer
Frequently Asked Questions (FAQs) - 12 Hallmarks of Aging
1) Can aging be slowed down?
Yes, scientific research suggests that lifestyle changes, dietary interventions, and targeted supplementation can help slow down certain aging processes. Strategies like intermittent fasting, caloric restriction, exercise, and compounds such as resveratrol, NAD+ boosters (NR/NMN), fisetin, and quercetin may support longevity and cellular health.
2) What are the 12 Hallmarks of Aging?
The 12 Hallmarks of Aging are biological processes that contribute to aging and age-related diseases. These include Genomic Instability, Telomere Attrition, Epigenetic Alterations, Loss of Proteostasis, Deregulated Nutrient Sensing, Mitochondrial Dysfunction, Cellular Senescence, Stem Cell Exhaustion, Altered Intercellular Communication, Disabled Macroautophagy, Chronic Inflammation (Inflammaging), and Dysbiosis (Gut Microbiome Imbalance).
3) What are the best supplements for aging?
The best supplements for aging depend on which hallmark of aging you are targeting. Some science-backed longevity compounds include:
- DNA & Telomere Support: Cycloastragenol, Astragaloside IV
- Cellular Energy & Mitochondrial Health: NR, NMN, Quercetin
- Senolytics (Clearing Senescent Cells): Fisetin, Quercetin
- Autophagy & Cellular Cleanup: Resveratrol, Spermidine
- Gut Microbiome & Inflammation: Probiotics, Fermented Foods
4) How does cellular senescence impact aging?
Cellular senescence occurs when cells stop dividing but remain metabolically active, releasing inflammatory compounds that accelerate aging. Senolytic compounds like fisetin and quercetin help remove these dysfunctional cells, reducing inflammation and promoting healthier aging.
5) What role does NAD+ play in aging?
NAD+ is a crucial coenzyme involved in cellular energy production and DNA repair. As we age, NAD+ levels decline, leading to mitochondrial dysfunction and reduced cellular repair mechanisms. Supplementing with Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN) helps restore NAD+ levels and supports healthy aging.
6) Can diet affect the hallmarks of aging?
Yes! Certain dietary approaches can influence aging:
- Intermittent Fasting & Caloric Restriction activate autophagy, helping remove damaged cellular components.
- Polyphenol-rich foods (e.g., blueberries, green tea, dark chocolate) support epigenetic regulation and inflammation reduction.
- Fermented foods improve gut microbiome balance, helping prevent dysbiosis and chronic inflammation.
7) How does mitochondrial dysfunction accelerate aging?
Mitochondria are the energy factories of our cells. As they lose efficiency with age, this leads to fatigue, oxidative stress, and cell damage. Compounds like CoQ10, NR/NMN, Quercetin, and Astragaloside IV support mitochondrial function and may improve energy levels.
8) What is inflammaging, and how can it be reduced?
Inflammaging refers to chronic, low-grade inflammation that occurs with age, contributing to diseases like Alzheimer’s, heart disease, and metabolic disorders. Anti-inflammatory interventions include curcumin, resveratrol, quercetin, omega-3s, and a Mediterranean diet.
9) How does gut health influence aging?
The gut microbiome plays a major role in immune function, inflammation, and brain health. Dysbiosis (an imbalance in gut bacteria) can accelerate aging. Supporting gut health with prebiotics, probiotics, fiber-rich foods, and fermented foods can help maintain microbiome balance and support longevity.
10) What is autophagy, and why is it important for aging?
Autophagy is the body’s natural cellular cleanup process, where it removes damaged proteins and dysfunctional cells. This process declines with age, leading to waste buildup. Fasting, ketogenic diets, spermidine, resveratrol, and astragaloside IV are known to enhance autophagy.
11) Are telomeres really the key to longevity?
Telomeres are protective caps at the ends of chromosomes that shorten over time, leading to cellular aging. Longer telomeres are associated with longevity. Telomerase-activating compounds like cycloastragenol and astragaloside IV may help maintain telomere length.
12) What lifestyle habits can support longevity?
To slow aging and support longevity, consider:
- Exercise regularly – especially resistance training and cardio.
- Practice intermittent fasting to activate autophagy.
- Eat an anti-inflammatory diet with polyphenol-rich foods.
- Prioritize sleep to support cellular repair.
- Use science-backed supplements targeting hallmarks of aging.