Aging is one of the great puzzles of our lifetime. Many of the world’s top minds work around the clock to answer a question…
Why do we age, and what can we do about it?
Scientists have attempted to piece together what wears our bodies down over time.
We call these pieces of the puzzle the “hallmarks of aging.”
Each piece provides clues on how to live longer, healthier lives. Ideally, we’ll reach a point where we can slow down or even reverse aging. That’s what scientists are working towards, and every day, they’re getting a bit closer to making it a reality.
In this post, I’ll share the currently recognized official hallmarks of aging. That way, you can focus on improving the one that’ll benefit your unique lifestyle most.
Note that this list is constantly growing, and I suspect it’ll eventually reach dozens of factors. For now, however, we have 12.
What Are The Latest Hallmarks of Aging?
Our bodies change dramatically as we get older.
Scientists work hard to determine the actual causes of aging itself (as opposed to the countless factors that change as a result of aging).
There’s no one golden theory or mechanism that explains all of aging Share on XYet addressing the latest hallmarks of aging could be the key to unlocking longevity. Each newly discovered hallmark offers fresh paths for research and potential treatments.
Until recently, experts proclaimed 9 hallmarks; Now, there are 12. This is big news because it means we know more about aging than ever.
Here’s a quick list of the latest 12 hallmarks of aging:
- Genomic instability
- Telomere attrition
- Epigenetic alterations
- Loss of proteostasis
- Deregulated nutrient sensing
- Mitochondrial dysfunction
- Cellular senescence
- Stem cell exhaustion
- Altered intercellular communication
- Inflammaging
- Disabled macroautophagy
- Microbiome dysbiosis
For example, we know that lifestyles/habits—like dietary restriction—influence the rate of aging. As does the consumption of certain nutrients. So does our activity level.
It’s not all about your genes; your daily choices matter too.
Understanding your rate of aging is crucial. It’s different for everyone. Factors like environment, lifestyle, genetics, epigenetics, etc. all play a part.
By studying these, we’ll learn how to slow biological aging, understand the root causes of health issues, and increase our overall health and health span.
The aging process decade by decade
Each chronological (calendar) decade of our life brings its own set of changes that affect how we age.
These changes are influenced by things like what we eat and how fast our bodies age. Scientists use animal models to study these changes. This helps them understand aging better.
Age 20-30
At this stage, you perform at your peak physically, have high metabolic rates, and efficient cell regeneration.
Collagen and elastin production are at their highest levels, maintaining skin elasticity and suppleness.
The immune system is robust, providing strong protection against infections. Telomeres, the protective caps at the end of chromosomes, are long and stable.
Basically, your body is in its prime.
Age 30-40
In the third decade of life, subtle signs of aging start to emerge as collagen synthesis decreases, leading to the formation of fine lines and early wrinkles.
The metabolic rate begins to decline slightly, affecting energy levels and body weight. Muscle protein synthesis declines, and fat accumulation starts to increase.
Cellular repair mechanisms become less efficient, resulting in longer recovery times from injuries or stress. Hormonal dysregulation becomes more pronounced.
Age 50-60
During this period, noticeable aging effects become apparent. Muscle mass decreases, contributing to decreased strength and agility.
Skin loses elasticity due to reduced collagen production, resulting in sagging and wrinkles.
Hormonal changes, such as menopause in women, accelerate loss of bone density loss, frailty, and increased risk of osteoporosis.
Cognitive performance starts to decline, affecting your memory and processing speed.
Age 70-80
In these years, organ function declines significantly. Impaired metabolism further accelerates aging.
The cardiovascular system weakens, leading to reduced cardiac output and increased risk of heart disease.
Lung capacity decreases, impacting respiratory function and exercise tolerance. Joint stiffness and decreased mobility become more common due to cartilage wear and tear.
Immune function weakens, making you more susceptible to infections and autoimmunity.
Physical degeneration often outpaces cognitive decline.
Age 90+
Reaching this advanced age is a testament to longevity. However, organ systems experience a severe decline in function.
The brain undergoes significant atrophy, affecting memory, cognition, and motor skills. Reduced kidney function impairs waste removal and fluid balance regulation. Lungs stop detoxifying and metabolizing chemicals as effectively. Cellular waste accumulates and manifests physically.
Bone density reaches its lowest levels, increasing susceptibility to fractures. Sensory organs, such as vision and hearing, deteriorate further, impacting the quality of life.
The Core Hallmarks of Aging (Causes of Damage)
The science of aging is complex.
Although countless factors influence your rate of aging, several stand out as the “hallmarks”. These have the most research implicating them in the aging process.
Of the hallmarks, a select few have the biggest impact AND appear to sit upstream of other hallmarks.
Essentially, fix the core hallmarks, and the others will likely automatically improve as well.
Let’s start with the best-known and classical hallmark of aging. Unlike some of the others, these are considered the causes of damage.
1. Genomic instability (damaged DNA)
Our DNA is like the instruction manual for our bodies. But as we age, this manual gets some wear and tear, leading to “genomic instability”.
Our cells don’t function as well, which causes diseases and speeds up the aging process.
Major causes of genomic instability include exposure to harmful environmental factors, like radiation or toxins.
These damage our DNA, making it harder for our cells to repair themselves and stay healthy.
But there’s hope. Scientists are discovering ways to protect our DNA and fix damage when it happens.
To fight genomic instability, we should start by:
- Avoiding known causes of DNA damage (smoking or excess exposure to nn-EMF, radiation, or even UV light)
- Eating a diet rich in antioxidants to neutralize harmful molecules called free radicals
- Exercising regularly
- Taking supplements and nutraceuticals
2. Telomere attrition (unprotected DNA)
Telomeres are protective “caps” at the ends of our chromosomes (like the eyelets on shoe laces). With each cell division, these caps get a little shorter.
Once they become too short, the cell can’t divide (a state called replicative senescence).
This process, called telomere shortening, is a natural part of aging but accelerates from stress, smoking, and poor diet. Especially, from long-term nutrient deficiencies.
Telomere biology shows ways we can slow down telomere shortening or even reverse it.
Some of the top ways to offset or slow telomere attrition include:
- Stress management
- Minimizing chemical exposure
- Adequate sleep
- Physical activity
- Dietary supplements like omega-3 fatty acids, amino acids like taurine
- Peptides & bioregulators
3. Epigenetic alterations (silenced DNA)
Epigenetics describes the phenomenon of the way genes are expressed.
For example, what’s “on” and “off”. These influence how our genes work without changing the genes themselves.
Causing cells and tissues to function differently. As we age, these epigenetic changes accumulate, affecting our health and aging process.
Unlike our DNA sequence, we can reverse our epigenetic expression. Potentially resetting our gene expression to a more youthful state.
It’s a newer facet of research but is still promising. In fact, epigenetic tests are currently the best way to measure your biological age.
Factors that shape your epigenetic biology include:
- Diet
- Environment (especially pesticides, nnEMFs, and endocrine disruptors)
- Sleep
- Stress
- Exercise
- Genetics (MTHFR)
- Methyl donor supplementation
- Supplements like green tea, resveratrol, pterostilbene, turmeric, NAD+ precursors
- Lifestyle vices
4. Loss of proteostasis (malfunctioning proteins)
Proteins are the workhorses of your body. They’re responsible for all kinds of functions.
As you age, your body’s ability to maintain protein homeostasis or proteostasis, starts to falter.
Proteins begin to fold incorrectly or clump together, leading to a range of age-related diseases. Like a factory with broken quality control mechanisms.
Your body has a built-in cleanup crew designed to handle these protein mishaps. But with age, this crew becomes overwhelmed and understaffed.
Resulting in a buildup of damaged proteins that wreak havoc on cell function.
To improve protein-folding homeostasis, you’ll want to activate heat shock proteins:
- Sauna and ice baths
- Exercise
- Calorie restriction
- Autophagy enhancers (spermidine, urolithin-A)
- Other supplements (GlyNAC, turmeric)
Metabolic & Bioenergetic Hallmarks (Responds to Damage)
Your metabolism and energy production systems also decline with age.
Unlike the core hallmarks, these are more downstream.
The savvy longevity biohacker first prioritizes the previous four primary hallmarks. Fixing those also improves these antagonistic hallmarks.
Nevertheless, the following four causes of aging still warrant attention.
5. Deregulated nutrient sensing (misused resources)
Your body’s ability to sense and respond to nutrients is like a complex network of traffic signals, directing cell growth and energy use. As you’d expect, this process becomes less efficient with age.
A wide variety of signals, pathways, and mechanisms comprise this hallmark, including:
- Insulin and insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway
- Mechanistic target of rapamycin (mTOR) pathway
- AMP-activated protein kinase (AMPK) pathway
- Sirtuins
Your body uses these among many others to determine how to best respond to nutrient levels.
Deregulation of these nutrient-sensing pathways causes metabolic imbalances, elevated oxidative stress, and greater cellular damage.
Scientists are uncovering ways to tweak these nutrient pathways back towards youthfulness.
Some of the top interventions to target the nutrient-sensing aging hallmarks include:
- Exercise
- Caloric restriction (without malnutrition)
- Methionine/protein restriction
- Intermittent fasting (IF) and time-restricted eating (TRE)
- Sirtuin activation (resveratrol, pterostilbene)
- NAD+ precursors (NR, NMN, NAD3, niacin, niacinamide)
- AMPK activators (berberine, ALA, quercetin, metformin)
- mTOR inhibitors (rapamycin, EGCG, turmeric, quercetin, resveratrol)
6. Mitochondrial dysfunction (low power)
Mitochondria generate all the cellular energy required to power every single bodily function and process. Without them, you’d die almost instantaneously.
Plus, their health also determines how much “cellular exhaust” your body must process and dispose of.
Dysfunctional mitochondria don't just contribute to aging; they're at the heart of it Share on XWhen they falter, it affects everything from your skin to your brain.
Some of the top ways to improve the mitochondrial dysfunction aging hallmark include:
- Exercise
- Caloric restriction
- Coenzyme Q10 supplementation
- NAD+ precursors (nicotinamide riboside)
- Antioxidants (MitoQ, SkQ1)
- Pyrroloquinoline quinone (PQQ) supplementation
- Alpha-lipoic acid
- L-carnitine
- Resveratrol
- Spermidine
- Methylene blue
- Red light therapy
- Ketogenic diet
- Fasting or intermittent fasting
- Polyphenols
- Creatine Monohydrate
Mitochondria are intricately tied to not just your aging, but your quality of life and performance. I suggest you check out my biohacker’s ultimate guide & tips to optimizing your mitochondria.
7. Cellular senescence (zombie cells)
Eventually, some cells become “zombies”. They enter a state known as senescence where they stop dividing and being useful but don’t die off. That’s not all.
Senescent cells also secrete harmful pro-inflammatory factors that “infect” nearby cells. Causing them to stop working normally.
Overall, this leads to a buildup that drives aging and disease.
So why does this body have this mechanism? Initially, senescence prevents damaged cells from replicating. Thus preventing the spread of cancer.
The cellular senescence switch gets triggered by all kinds of things. Such as DNA damage, excess oxidative stress, and the shortening of telomeres.
Many of which are primary hallmarks. Plus, cancerous signals may cause senescence too.
This is a newer hallmark of aging, and the current treatments look incredibly promising.
In fact, you can safely and effectively use senolytic supplement complexes to practice this therapy from the comfort of your home.
Some of the top ways of clearing senescent cells include:
- Senolytics (dasatinib, quercetin, piperlongumine)
- Senostatics (fisetin, curcumin, metformin)
- Immunomodulation
- Polyphenol consumption
- Regular physical exercise
- Caloric restriction
- Intermittent fasting
- Telomerase activators (TA-65, astragalus, epitalon)
- mTOR inhibitors (rapamycin)
- NAD+ boosters
- Stem cell therapy
Integrative Hallmarks (Outcome of the Damage)
Now, we have the final set.
Scientists sometimes refer to them as the “integrative hallmarks”.
We can see the results of biological aging as measured by these processes. They indicate issues with the previous seven.
Nonetheless, we can and should still optimize these ones too.
8. Stem cell exhaustion (lacking supercells)
Stem cells are the body’s raw materials, capable of turning into other cell types to repair, maintain, or build tissues.
As you age, you deplete your reserves of these special cells. These stem cells start to wear out, a process logically called “stem cell exhaustion”.
This partially occurs due to telomere shortening, which occurs each time a cell divides. But it’s also caused by DNA damage, inflammatory signals, microenvironment changes, and other epigenetic changes.
Researchers are exploring ways to rejuvenate stem cells to combat exhaustion.
In aged mice, interventions that protect against telomere shortening or promote cell cycle progression have shown promise in restoring stem cell function.
This not only highlights the importance of stem cells in tissue regeneration but also presents a good target for anti-aging therapies.
By tackling stem cell exhaustion, we could significantly enhance our body’s ability to repair itself and age more gracefully.
The best strategies to counteract stem cell exhaustion include the ones for the previous hallmarks. Plus:
- Anti-inflammatory therapies
- Stem cell transplantation
- Stem cell activation biohacks
- Hormone optimization
9. Altered intercellular communication (bad signals)
Cells rely on an intricate communication system. Issues arise with the slightest disruption to the signals cells send to each other to maintain health and function. Tissues and organs stop functioning optimally and consume too much energy.
Altered intercellular communication leads to chronic inflammation (”inflammaging”), and eventually to age-related diseases. This mostly occurs due to negative changes in the immune system and the cellular environment.
The best interventions to fix altered intercellular communication include:
- Anti-inflammatory protocols
- Cytokine balancers
- Exosome therapy
- Gut microbiome health
- Peptides
- Hormone optimization
- EGCG
- Quercetin
10. Inflammaging (inflammation-induced aging)
Inflammaging refers to the chronic, low-grade inflammation.
This isn’t the acute inflammation you experience when you get a cut or catch a cold. Instead, it’s a slow, simmering state that undermines your health.
“Every disease relates to inflammation”
-Hippocrates
Over long periods, it contributes to the development of age-related diseases like arthritis, diabetes, and heart disease.
The causes of inflammaging are complex. Some include changes in the immune system, poor diet, lack of exercise, stress, environmental toxins, accumulation of senescent cells, impaired mitochondrial function, and alterations in the gut microbiome.
Some of the top ways to combat inflammaging:
- Anti-inflammatory protocols
- Cytokine balancers
- Balancing omega-3 and omega-6 fatty acids
- Polyphenols-rich diet
- Probiotics
- Exercise
- Stress reduction
- Caloric restriction
- Antioxidants
- Sleep
- Quitting lifestyle vices (smoking, alcohol)
- Herbals (ginger, turmeric, green tea, and garlic)
We should highlight the consumption of polyphenol-rich food. It’s an underrated way to combat inflammaging and it’s also easy to incorporate these food sources to your diet. Find out more in my full guide to polyphenols.
11. Adaptive immunosuppression (declining immunity)
Our immune systems work great when we’re young to keep us healthy and thriving. The immune system has two distinct branches: innate and adaptive.
As the name implies, the adaptive immune system responds to everyday life challenges. Just like the other hallmarks, the effectiveness of the adaptive immune system dwindles over time.
Two types of cells, T Cells and B Cells, fare especially poorly.
Partially because the structures associated with their development and maturity decline with age. Resulting in greater incidences of infections as well as autoimmunity.
Most of the strategies for this hallmark are very experimental, and I’m not comfortable listing them.
Some of the basic ways to target adaptive immunosuppression include:
- General health & wellness activities
- “Thymus thumping”
- Peptides, particularly TA-1
- Anti-inflammatories
- Exercise
- Senolytics
- Echinacea
- Astragalus
- Adaptogenic, functional medicinal mushrooms
- Stress reduction
12. Macroautophagy decline (cleanup issues)
Macroautophagy (usually just called “autophagy”) is the fancy word for cellular repair. It’s the crucial process of cleaning out damaged cellular components.
This process becomes less efficient as you age and leads to the accumulation of cellular debris and dysfunctional proteins. Which causes inflammation, and the progression of age-related diseases.
Many of the popular longevity supplements today claim to target and improve this particular process.
The related term “mitophagy” refers to a similar process taking place specifically in the mitochondria.
Some of the top ways to fix macroautophagy decline include:
- Caloric restriction
- Exercise
- Pharmacologics ( rapamycin)
- Diet (fasting, ketogenic diet)
- Lifestyle (managing stress, adequate sleep)
- Antioxidants
- AMPK activators
- Sirtuin activators
- Autophagy-inducing peptides
- Chaperone-mediated autophagy enhancers
- mTOR inhibitors
- Proteasome activators
Beyond the 12 Hallmarks to Optimize The Biological Aging Process
When you dive into the world of aging, you’ll find the journey goes way beyond just the currently accepted 12 hallmarks.
Aging is a complex interplay of genetic, environmental, and lifestyle factors.
No single factor comes close to explaining all aspects of aging, and no one-size-fits-all solution can stop it. Trying to target one particular pathway or using just one single intervention will always fail to translate into real-world meaningful results.
Smart longevity hackers will scroll through this list of contributors to the aging process, and find the interventions that impact the most hallmarks.
It’s no coincidence that these are also the tenets of integrative holistic health.
The aging process works like a symphony, not a solo performance. Every part of your body must work in harmony to slow the biological aging process.
Despite the fanciest technologies, we still can’t really target any single hallmark specifically. Every intervention creates a cascade of aging (or anti-aging) signals throughout the body.
Every decision, habit, and behavior of yours matters.
That’s why I created a mini 14-day longevity challenge to help you do exactly that. You can certainly skip the prohibitively expensive, flashy anti-aging biohacks and quickly optimize yourself in just a few minutes per day.
This mini-course arms you with the highest-impact longevity tactics, validated by the latest research and time-proven by the world’s ancient medical systems.
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