The science of aging has advanced dramatically over the last decade. Instead of viewing aging as a single process, researchers now see it as a collection of interconnected biological mechanisms that gradually impair our cellular function, known as the 12 hallmarks of aging. It helps scientists understand why we age and how we can promote healthy aging.
They can be divided into three categories:
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The primary hallmark is the underlying cause of cellular damage
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Antagonistic characteristics are the reaction to damage that can become harmful when dysregulated.
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Integrative hallmarks are the ultimate outcomes driving tissue and organismal decline
The 12 Characteristics of Aging
The following hallmarks build on this framework to show how aging occurs at the cellular level. Although each hallmark describes a distinct biological process, they function as an interconnected system, which means that dysfunction in one area can affect another. This cascading effect is a major reason why aging accelerates over time, and interventions that target fundamental cellular pathways can have far-reaching, systemic benefits.
As researchers gain a better understanding of these mechanisms, they are identifying ways to promote healthier aging by strengthening the body's natural repair systems, increasing metabolic efficiency, and maintaining cellular resilience. Interventions like NMN and NAD⁺-supporting compounds are gaining attention for their potential impact on multiple hallmarks. These approaches are being investigated for their potential to reduce some of the most significant drivers of biological aging by restoring cellular energy, improving stress-response pathways, and increasing DNA repair capacity.
1. Genomic Instability
Definition: Genomic instability is the accumulation of DNA damage.
Every day, our cells are subjected to various forms of genetic damage, including oxidative stress, environmental toxins, metabolic byproducts, and replication errors. Over time, this damage accumulates faster than the body can repair it, leading to cellular dysfunction and disease risk.
Potential NMN link: Enzymes that repair DNA, such as sirtuins and PARPs, require NAD⁺. While sirtuins assist in preserving genome stability and controlling stress reactions, PARPs identify and signal DNA damage, enlisting other proteins to fix broken strands. Our repair systems become less effective as we age due to a reduction in NAD⁺ levels. This keeps these enzymes active and promotes more efficient DNA repair by raising NAD⁺ through NMN.
2. Telomere Attrition
Definition: With every cell division, the protective caps (telomeres) on chromosomes shorten.
Although telomeres function as "biological buffers," they eventually naturally shorten. Cellular aging and senescence are caused by critically short telomeres.
Potential NMN link: NAD⁺-dependent sirtuins aid in controlling the stability and structure of telomeres. By increasing the availability of NAD⁺, NMN may indirectly aid in telomere maintenance.
3. Epigenetic Alterations
Definition: Variations in gene expression that are not brought about by modifications to the DNA sequence.
The epigenetic markers that determine when genes should be turned "on" or "off" are disrupted by aging. These alterations lead to cellular identity loss and heightened susceptibility to age-related illnesses.
Potential NMN link: Sirtuins and other epigenetic regulators rely on NAD⁺. Maintaining more stable gene-expression patterns may be aided by NMN-supported proper NAD⁺ levels.
4. Loss of Proteostasis
Definition: A reduction in cells' capacity to preserve the proper folding, shape, and functionality of their proteins.
As people age, misfolded or damaged proteins build up, stressing cells and causing neurodegeneration and other long-term illnesses.
Potential NMN link: Healthy NAD⁺ levels support mitochondria and stress-response proteins that help maintain proteostasis.
5. Disabled Macroautophagy
Definition: Decreased cellular "clean-up" procedures that eliminate waste and damaged parts.
Recycling outdated or damaged cell components depends on autophagy. Damaged components build up and hinder cellular function when autophagy slows down with age.
Potential NMN link: NAD-dependent enzymes play a role in the regulation of autophagy. Encouraging NAD⁺ could improve cellular repair and recycling processes.
6. Deregulated Nutrient-Sensing
Definition: Changes in nutrient sensing and response pathways have an impact on metabolism and energy balance.
With age, key pathways such as insulin/IGF-1, AMPK, mTOR, and sirtuins become dysregulated, interfering with metabolic function.
Potential NMN link: NAD⁺ plays a key role in sirtuin activity, which regulates nutrient sensing and metabolism. According to studies, NMN may help improve metabolic responses and insulin sensitivity.
7. Mitochondrial Dysfunction
Definition: When mitochondrial function declines, energy production decreases.
Mitochondria generate cellular energy (ATP). Aging reduces their efficiency, raises oxidative stress, and decreases cellular resilience.
Potential NMN link: NAD⁺ is necessary for mitochondrial energy production. According to studies, NMN supplementation can improve energy metabolism and mitochondrial function.
8. Cellular Senescence
Definition: A state in which cells stop dividing and produce inflammatory molecules.
Senescent cells accumulate with age and secrete harmful factors (the SASP), hastening tissue decline and inflammation.
Potential NMN link: NAD⁺-dependent enzymes impact senescence pathways and cellular stress responses. NMN may promote healthy cell turnover and delay stress-induced senescence.
9. Stem Cell Exhaustion
Definition: A decrease in stem cell ability to divide and differentiate.
Stem cells play an essential role in tissue repair and regeneration. As they age, their function and numbers deteriorate, slowing healing and contributing to tissue breakdown.
Potential NMN link:
Research suggests that NAD⁺ pathways support stem cell metabolism and regenerative capacity. Supporting NAD⁺ with NMN could promote healthy stem cell environments.
10. Altered Intercellular Communication
Definition: Changes in how cells communicate using signalling molecules and networks.
Aging disrupts the normal communication between cells and tissues, which contributes to immune decline, hormonal changes, and inflammation.
Potential NMN link: NAD⁺ regulates immune cell function and signaling. NMN's support for NAD⁺ levels may improve communication between cells and systems.
11. Chronic Inflammation
Definition: A chronic, low-level inflammation state.
Chronic inflammation accelerates biological aging and contributes to nearly every major age-related disease, including heart disease, Alzheimer's, and diabetes.
Potential NMN link: NMN may contribute to a healthier inflammatory balance by improving mitochondrial efficiency and cellular repair systems.
12. Dysbiosis
Definition: Disruption in microbial communities in the gut and other parts of the body.
Aging reduces good microbial diversity while increasing harmful bacteria. This affects immunity, metabolism, and overall health.
Potential NMN link: Although this field is still in its infancy, new research suggests that NAD⁺ metabolism may have an impact on microbial balance and gut barrier integrity.
How Does NMN Fit Into the Bigger Picture
Aging symptoms often indicate a decrease in NAD⁺ levels. By middle age, NAD⁺ decreases by up to 50%, which continues throughout life. Many of the previously mentioned characteristics are impacted by this decline because NAD⁺ is necessary for DNA repair, mitochondrial function, metabolic signaling, and cellular resilience.
By restoring NAD⁺ availability, NMN can support:
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Cellular energy production
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DNA repair efficiency
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Proper gene expression
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Autophagy and cellular cleanup
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Metabolic and nutrient-sensing pathways.
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Immune and inflammatory balance.
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Stem cell activity and tissue regeneration
References:
“NAD⁺ and Sirtuins in Aging and Disease” — a 2013 review article
“The therapeutic perspective of NAD⁺ precursors in age-related diseases” (2024)
