ACEND

The 14 Hallmarks of Aging — And How ACEND® Addresses Them

Date: October 2, 2025
Contributing Authors: Team TRILITY / ACEND

Aging is the most universal of human experiences, yet modern science increasingly views it not as an inevitable decline but as a process with defined biological mechanisms. In 2013, López-Otín and colleagues proposed the original “9 Hallmarks of Aging,” which became the cornerstone framework for understanding how cells and systems deteriorate over time. Since then, advances in biogerontology have expanded the model to 14 hallmarks, reflecting the complexity of molecular and cellular aging.

Understanding these hallmarks is more than academic—it allows us to identify interventions that slow, modulate, or even reverse aspects of aging biology. This is where targeted nutritional therapeutics, like ACEND®, come in. ACEND® is a patented medical food designed with evidence-based bioactives, polyphenols, and micronutrients to help restore balance across multiple biological systems. By addressing chronic inflammation, mitochondrial decline, and impaired intercellular communication, ACEND® supports resilience at the core of aging biology.

In this article, we’ll break down the 14 hallmarks of aging and explore how ACEND® is positioned to help address them.

The 14 Hallmarks of Aging

1. Genomic Instability

Accumulated DNA damage and mutations impair cellular function. Radiation, toxins, and oxidative stress accelerate this process.

ACEND® Connection: Polyphenols like quercetin and dihydroquercetin, as well as NAC (N-acetyl cysteine), act as powerful antioxidants and DNA-protective agents, reducing oxidative damage at the genomic level.

2. Telomere Attrition

Telomeres, the protective caps on chromosomes, shorten with every cell division. Short telomeres are linked to aging and chronic disease.

ACEND® Connection: CurcuRouge® (bioavailable curcumin) and luteolin are linked to reduced oxidative stress and lower telomeric shortening through NF-κB pathway modulation.

3. Epigenetic Alterations

DNA methylation, histone modification, and chromatin remodeling drift with age, altering gene expression.

ACEND® Connection: Polyphenolic compounds (e.g., proanthocyanidins from grape seed) have epigenetic-modifying potential, helping maintain youthful gene expression patterns.

4. Loss of Proteostasis

Proteins lose their correct folding and accumulate as aggregates (amyloids, tau tangles), impairing cellular function.

ACEND® Connection: Astaxanthin and epicatechins support proteostasis by reducing protein misfolding and promoting autophagy.

5. Disabled Macroautophagy

Cells lose efficiency in “cleaning out” damaged organelles and proteins, which accelerates degeneration.

ACEND® Connection: Urolithin A (a metabolite promoted by grape seed polyphenols) stimulates mitophagy, enhancing cellular “clean-up” mechanisms.

6. Deregulated Nutrient Sensing

Pathways like mTOR, AMPK, and sirtuins lose their balance, leading to metabolic dysfunction.

ACEND® Connection: Quercetin, epicatechins, and betaine help optimize nutrient sensing by modulating AMPK activation and mTOR signaling.

7. Mitochondrial Dysfunction

Declining mitochondria impair energy metabolism and increase ROS (reactive oxygen species).

ACEND® Connection: Dihydromyricetin, astaxanthin, and magnesium support mitochondrial biogenesis, reduce oxidative leakage, and improve ATP output.

8. Cellular Senescence

Old, “zombie” cells accumulate and secrete pro-inflammatory SASP (senescence-associated secretory phenotype) factors.

ACEND® Connection: Quercetin is a well-studied senolytic compound, selectively helping clear senescent cells. Boron and luteolin also modulate SASP signaling.

9. Stem Cell Exhaustion

With age, stem cells lose regenerative capacity, impairing tissue repair.

ACEND® Connection: Curcumin and epicatechins enhance stem cell function by reducing oxidative load and improving regenerative signaling.

10. Altered Intercellular Communication

Cells stop “talking” properly, driving chronic inflammation and immune aging.

ACEND® Connection: Bacillus coagulans (LactoSpore®) supports gut-immune communication, while polyphenols like proanthocyanidins enhance intercellular signaling fidelity.

11. Microbiome Disturbance (Dysbiosis)

Gut microbial imbalance promotes inflammation, metabolic dysfunction, and neurodegeneration.

ACEND® Connection: LactoSpore® probiotic restores balance, while polyphenols act as prebiotics, feeding beneficial microbes.

12. Chronic Inflammation (“Inflammaging”)

Low-grade, systemic inflammation drives nearly every age-related disease.

ACEND® Connection: ACEND®’s core purpose is to reduce chronic inflammation. CurcuRouge®, Nigellin® black cumin seed extract, luteolin, and astaxanthin all directly suppress inflammatory cytokines (IL-6, TNF-α, NF-κB).

13. Compromised Autonomic Nervous System Function

Aging alters the balance of sympathetic and parasympathetic tone, impairing systemic regulation.

ACEND® Connection: Polyphenols improve vascular tone and endothelial function, while magnesium and potassium support autonomic balance.

14. Altered Mechanical Properties of Cells

With age, cells lose structural integrity, contributing to vascular stiffness, fibrosis, and organ dysfunction.

ACEND® Connection: Boron, magnesium, and calcium help maintain extracellular matrix integrity, while antioxidants reduce stiffening by lowering glycation and oxidative cross-linking.

Why ACEND® Matters

Aging is multifactorial, and no single intervention can address all hallmarks. What makes ACEND® unique is its systems-based approach. Instead of targeting only one hallmark, ACEND® brings together clinically validated compounds to synergistically influence all 14 hallmarks of aging:

  • CurcuRouge® bioavailable curcumin — anti-inflammatory, genomic protector, telomere support.
  • Quercetin + dihydroquercetin — senolytic activity, DNA protection, vascular support.
  • Epicatechins (green tea extract) — nutrient sensing modulation, mitochondrial protection.
  • Astaxanthin (AstaFerm®) — proteostasis, antioxidant powerhouse, vascular health.
  • Nigellin® black cumin extract — potent NF-κB modulation, systemic inflammation reduction.
  • Bacillus coagulans (LactoSpore®) — gut microbiome restoration, immune regulation.
  • Boron, magnesium, calcium, potassium — bone, muscle, vascular, and nervous system balance.

By addressing multiple hallmarks simultaneously, ACEND® helps restore balance where aging biology goes off course.

 

References

  1. López-Otín C, et al. The hallmarks of aging. Cell. 2013;153(6):1194-1217.
  2. López-Otín C, Kroemer G. Hallmarks of health. Cell. 2021;184(1):33-63.
  3. Kennedy BK, et al. Geroscience: Linking aging to chronic disease. Cell. 2014;159(4):709-713.
  4. Singh CK, et al. Impact of polyphenols on aging and age-related diseases. Nutrients. 2019;11(9):2063.
  5. Zhou Y, et al. Curcumin, quercetin, and aging-related pathways: Molecular insights. Front Aging Neurosci. 2022;14:880250.
  6. Martín-Pardillos A, et al. Epicatechin as a mitochondrial modulator in aging. Redox Biology. 2020;36:101659.
  7. Tan BL, Norhaizan ME. Curcumin and age-related diseases: Nutrigenomic insights. Nutrients. 2019;11(12):2959.

Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.