The 12 Hallmarks of Aging – Understanding the characteristics of aging

What are the Hallmarks of Aging?

When it comes to aging, many people initially think of gray hair, wrinkles, or declining energy. But aging begins at the cellular level. Scientists have discovered twelve fundamental biological processes—the so-called Hallmarks of Aging—that are responsible for our bodies losing function over time. Originally, nine such Hallmarks were defined in 2013; in 2023, the list was expanded to a total of twelve. These describe how and why our cells and organs function less efficiently with age. Understanding these "root causes of aging" is crucial because we can only specifically influence what we know.
The bottom line is: We are not helpless against aging. Recent research shows that a healthy lifestyle, fasting, or exercise can slow many of these aging processes. Modern longevity supplements also aim to positively influence several of these hallmarks simultaneously. Below, you'll learn about the twelve hallmarks of aging, what they mean, and how you can potentially slow or mitigate them—for example, through lifestyle or targeted active ingredients.

The 12 characteristics of aging at a glance

1. Genomic instability (DNA damage)

Our DNA is like the body's blueprint. Over the years, however, damage accumulates in our genetic material – caused by UV radiation, environmental toxins, or simply errors during cell division. In our younger years, the body is still able to repair such defects well; however, with age, the error rate and repair fatigue increase. The result of genomic instability are mutations that can lead to loss of cell function and diseases (including cancer). Measures include protection from excessive UV radiation, sufficient sleep (for DNA repair phases), and nutrients such as NAD+ boosters to support repair enzymes.

2. Telomere shortening

At the end of our chromosomes are telomeres – protective caps of the DNA that shorten a little with each cell division. If a telomere becomes too short (known as the Hayflick limit), the cell can no longer divide and becomes dysfunctional. Telomere shortening is thus a built-in clock for cell division and aging. Measures: Chronic stress and inflammation accelerate telomere loss, while a healthy lifestyle (exercise, stress management) can slow the loss. Approaches such as telomerase activators (enzymes that could lengthen telomeres again) are also under research. Adequate selenium intake also contributes to reducing DNA damage and slowing cell aging caused by telomere shortening.

3. Epigenetic changes

Epigenetics controls which of our genes are switched on or off – similar to markers in our DNA book that determine which chapters are read. With age, this gene activity becomes misregulated because epigenetic markers are lost or located in the wrong places. As a result , some programs in older cells run incorrectly , which can contribute to age-related diseases such as cancer or metabolic disorders. Measures: Some nutrients and cofactors (e.g. methyl group donors like folate or betaine ) support normal DNA methylation and can thus mitigate epigenetic drift. Exercise and sufficient sleep also help to set the epigenetic clock more favorably.

4. Loss of proteostasis

Proteins are the workhorses of the cell. Proteostasis means that protein production, folding, and degradation remain in balance. With age, this balance declines – misfolded or defective proteins accumulate, while useful proteins may no longer be produced in sufficient quantities. The cell becomes "cluttered" and loses performance; diseases such as Alzheimer's and Parkinson's are associated with impaired proteostasis. Measures: Autophagy —the cellular "recycling program"—plays a role here. Fasting and regular exercise activate autophagy and help break down damaged proteins. Adequate protein intake and certain dietary supplements ( e.g., spermidine ) are also being discussed as ways to maintain protein homeostasis.

5. Deactivated macroautophagy (cellular recycling)

Autophagy is the body's "garbage disposal" process, by which cells degrade and recycle old components, waste products, or damaged organelles . With increasing age, autophagy activity declines . This means more cellular waste remains —e.g., defective mitochondria or clumped proteins—which further impairs cellular function. Impaired autophagy is associated with age-related diabetes, neurodegenerative diseases, and general loss of cellular function. Measures: Fasting is the most natural way to boost autophagy—even 16 hours without food increases cellular recycling. Certain supplements such as nicotinamide riboside (NR) or urolithin A are considered autophagy boosters , which can restart the degradation process. Regular exercise also plays a role here, as exercise has been shown to stimulate autophagy in muscles and organs.

6. Deregulated nutrient perception

Our cells have sensors for nutrients like glucose or amino acids to control growth or energy-saving programs . As we age, this nutrient sensing becomes disrupted – the mTOR signaling pathway is often permanently overactive, while AMPK is understimulated. This leads to constant cell growth at the expense of repair and autophagy. Measures: Caloric restriction (consuming fewer calories) or intermittent fasting can normalize these signaling pathways. Studies in mice, for example, show that 30% fewer calories can extend lifespan by up to 30%. Certain active ingredients (so-called calorie restriction mimetics such as alpha-ketoglutarate or resveratrol ) also mimic starvation and activate longevity enzymes such as sirtuins .

7. Mitochondrial dysfunction

Mitochondria are the "powerhouses" of our cells and produce energy (ATP). Over time, mitochondrial efficiency decreases – among other things, more electrons are lost in the respiratory chain and oxidative stress (harmful free radicals) increases . Damaged mitochondria produce less energy and can also emit inflammatory signals or initiate cell death. The result: reduced performance and increased cell damage from free radicals. Measures: Strength and endurance training are considered an effective way to keep mitochondria healthy—they stimulate the formation of new mitochondria. NAD+ precursors such as nicotinamide riboside can also support mitochondrial function, as NAD+ is essential for energy production. Antioxidants in the diet (e.g., from fruits/vegetables or quercetin ) help counteract free radicals.

8. Cellular senescence

Cells normally go through a constant cycle of division and renewal. Senescent cells, on the other hand, have reached the end of their division – they remain alive in the tissue but cease their normal function . On the one hand, senescence is a protective mechanism against cancer (cells with DNA damage stop dividing), and on the other hand, these “zombie cells” accumulate with age and release inflammatory messenger substances (SASP) that damage surrounding tissue. They thus contribute to chronic inflammation and tissue wear and tear. Measures: The body normally clears senescent cells through the immune system – but this works less well with age. This is where senolytics come into play: these are active ingredients that specifically kill senescent cells. A well-known example is quercetin , which has been shown in studies to reduce inflammatory markers in patients by eliminating senescent cells. Sufficient sleep and stress avoidance also have an indirect effect, as they reduce the accumulation of cell damage.

9. Stem cell exhaustion

Stem cells are our cell reserve - they can divide and develop into different cell types in order to renew used tissue. However, with age the stem cell pool becomes depleted : the ability of stem cells to divide decreases. Fewer fresh cells are produced, which slows down regeneration in bone marrow, skin or muscles, for example. The result: wounds heal more slowly, the immune system weakens (fewer new immune cells), and organs regenerate more poorly. Measures: your entire lifestyle plays a role here - no smoking , a balanced diet and exercise protect the stem cells. In medicine, work is being done on stem cell therapies (e.g. blood stem cell transfusions) to halt the signs of aging. Experiments have also shown that fasting is effective: autophagy induced by fasting can rejuvenate stem cells by breaking down old cell parts.

10. Altered intercellular communication

Our cells are constantly in contact via messenger substances. As we age, this signaling between cells shifts to the negative: The immune system releases more pro-inflammatory substances and monitors degenerated cells less effectively. Substances from aging tissues (e.g., fat cells or senescent cells) also have a damaging effect on other organs . For example, chronically elevated levels of interleukin-6 (an inflammatory messenger) can promote aging processes throughout the body. Measures: An anti-inflammatory diet (plenty of fruits, vegetables, and omega-3 fatty acids) and exercise help keep inflammation levels low. Senolytics (targeting the source of some signaling substances) or selenium are also interesting here, as selenium supports immune function and acts as an antioxidant, reducing cell damage caused by miscommunication.

11. Chronic inflammation (inflammaging)

" Inflammaging " refers to the condition in which the body's baseline inflammation levels are elevated with age. Even without an acute infection, constant mild inflammatory reactions occur – comparable to a smoldering fire in the body. The causes are diverse: for example, age-related deposits in blood vessels (which trigger immune reactions), senescent cells , a disturbed microbiome, or visceral fat tissue that secretes inflammatory factors. Inflammaging is associated with almost all age-related diseases (from arteriosclerosis to diabetes to Alzheimer's). Measures: Maintain a normal weight (reduces inflammatory belly fat), reduce stress (excess cortisol promotes inflammation), and consume anti-inflammatory nutrients . Antioxidants such as vitamin C, quercetin, and selenium are particularly effective here, as they neutralize free radicals and thus mitigate the chain reaction of inflammation. Studies have shown, for example, that selenium and other micronutrients strengthen the immune system and slow cellular aging by reducing oxidative stress and inflammatory activity.

12. Dysbiosis of the microbiome

Our gut is home to billions of beneficial bacteria (microbiome), which are important for digestion, immune defense, and nutrient production, among other things. With age, the composition of the intestinal flora often changes unfavorably – beneficial bacteria decrease, while inflammatory or pathogenic germs increase. This dysbiosis contributes to weakened immune defenses, chronic inflammation, and even mood swings (gut-brain axis). Measures: A fiber-rich diet promotes a healthy microbiome. Probiotics (good bacteria strains as a supplement) and fermented foods can help restore balance in the gut. Exercise also indirectly has a positive effect on the intestinal flora. Since a healthy microbiome influences inflammation and metabolism , maintaining it is increasingly recognized as an anti-aging strategy.

How can you positively influence the Hallmarks of Aging?

The good news: You can actively do something to slow down this aging process. Lifestyle is a powerful lever – people who eat a balanced diet, exercise regularly, get enough sleep, and reduce stress often age more slowly at the cellular level. Studies show, for example, that a consistent calorie-restricted diet reduces inflammation and can extend the lifespan of organisms. Regular exercise also improves many hallmarks simultaneously: It keeps mitochondria fit, reduces inflammation, and promotes autophagy (cellular cleansing).

In addition, science is shifting the focus to targeted supplements to address the hallmarks of aging. One example is Never Age Nutrition's Longevity Complex Revive —a supplement that combines five scientifically proven active ingredients to address the 12 main causes of aging. Let's take a closer look at these ingredients and their effects :

• Nicotinamide riboside (NR): A vitamin B3 derivative and NAD+ precursor. NR increases cellular NAD+ levels, which supports energy production and DNA repair in cells . Increased NAD+ also activates sirtuins —longevity-related enzymes that regulate genes for repair and metabolism. This positively influences hallmarks such as genomic instability, mitochondrial dysfunction, and deregulated metabolism.
• Calcium alpha-ketoglutarate (Ca-AKG): The stable form of α-ketoglutarate, a molecule involved in cellular metabolism (Krez cycle) that declines with age. A study in mice showed that Ca-AKG could extend health span – the treated animals lived longer and had fewer pro-inflammatory cytokines in their blood. Ca-AKG works similarly to calorie restriction by optimizing energy metabolism and reducing chronic inflammation (inflammaging). This is particularly helpful against mitochondrial dysfunction, inflammatory processes, and epigenetic dysregulation.
• Betaine (trimethylglycine): A natural methyl group donor that promotes methylation in the body . Adequate methyl groups are essential for protecting DNA structure and breaking down homocysteine ​​(a harmful metabolite). In fact, betaine can increase levels of S-adenosylmethionine (SAM) —the main methyl donor—thus counteracting age-related declines in methylation. Betaine also lowers homocysteine ​​levels, which helps prevent vascular and nerve damage. Studies also attribute betaine to improving mitochondrial function and muscle strength , as well as reducing inflammation. Overall, betaine supports hallmarks such as epigenetic stability, proteostatic balance, and a non-inflammatory cellular environment.
• Quercetin: A flavonoid found in many fruits and vegetables with remarkable anti-aging properties. Quercetin acts as an antioxidant and scavenges free radicals, thereby protecting DNA and mitochondria from oxidative stress. Quercetin is also a natural senolytic agent : It can drive aging, senescent cells to "suicide," or facilitate their degradation by the immune system. For example, studies have shown that quercetin combined with dasatinib reduced inflammation and tissue damage in aged animals and even humans. Thus, quercetin specifically targets the hallmarks of cellular senescence , chronic inflammation , and genomic instability (by reducing oxidative DNA damage).
• Selenium: An essential trace element known for numerous anti-aging functions . Selenium is central to antioxidant enzymes (such as glutathione peroxidase), which protect cells from oxidative stress. Adequate selenium intake contributes to reducing DNA damage and slowing telomere-shortening-induced cell aging. Studies show that selenium, along with vitamins, improves immune function in old age and can slow the biological aging clock . Selenium is also important for normal thyroid function and healthy immune protection , which indirectly benefits many hallmarks (e.g., reduced susceptibility to inflammation, improved cell communication, and maintenance of proteostasis through reduced oxidative stress).

Conclusion: The 12 Hallmarks of Aging offer an excellent overview of why we age – and at the same time show starting points for how we can influence the aging process. The sooner you start protecting your cells – through an antioxidant lifestyle, regular exercise, sufficient regeneration and targeted supplements such as Never Age Revive with NR, Ca-AKG, betaine, quercetin and selenium – the better you can prevent the signs of aging. While there is no universal fountain of youth elixir, science makes it clear that preventative measures at the cellular level have the potential to keep us vital, clear-headed and energetic for longer. Because ultimately, it is often the small molecular adjustments that we make in order to age gracefully – and in the best possible health.