There are 12 hallmarks of aging that are used to define aging. These hallmarks are deemed to be the characteristics of aging that scientists and researchers in the field of gerontology can use in their on longevity and healthspan research.
Why Do We Need to Define the Hallmarks of Aging?
Scientists now know that the rate of aging is influenced by genetics and biochemical pathways, but need common denominator characteristics between mammals, like us humans, to help see if interventions make any change to these hallmarks.
The study of why we age is gaining a lot more interest every passing year. I can see this growth in interest trend from the amount of research papers using the term aging in PubMed.
Also, there is a growing interest to study our biological age vs chronological age as part of healthy aging.
This is where a research paper published in the Journal Cell in 2013 from Carlos López-Otín et al. tried to define what are these common denominators that others can reference in their ongoing research.
Originally there were 9 hallmarks of aging, which was expanded to 12 hallmarks in their 2023 paper. An interesting fact is at a research symposium held in Copenhagen (Denmark) on the 22nd of March 2022 they came up with the 15 “New Hallmarks of Ageing”.
What Are the Twelve Hallmarks of Aging?
The 12 hallmarks of aging according to the research paper published in the Journal, Cell, are:
| Number | Hallmark | Short Description |
|---|---|---|
| 1 | Epigenetic Alterations | Changes in gene expression without altering the underlying DNA sequence. |
| 2 | Loss of Proteostasis | Disruption of the balance of protein synthesis, folding, and degradation in cells. |
| 3 | Deregulated Nutrient Sensing | A situation where certain proteins contribute to aging rather than longevity. |
| 4 | Mitochondrial Dysfunction | A condition where the mitochondria, responsible for producing energy in cells, do not function properly. |
| 5 | Cellular Senescence | A state of permanent cell cycle arrest that cells enter in response to various types of stress. |
| 6 | Stem Cell Exhaustion | The loss of the ability of stem cells to divide and differentiate into various cell types. |
| 7 | Altered Intercellular Communication | Changes in the way cells communicate with each other. |
| 8 | Genomic Instability | A variety of genetic changes that occur in a cell’s DNA. |
| 9 | Telomere Attrition | The process where the terminal caps of the chromosomes become shorter. |
| 10 | Dysbiosis | A condition of microbial imbalance caused by an overgrowth of “bad” bacteria inside the gut. |
| 11 | Chronic Inflammation | A persistent inflammatory response that can lead to tissue damage and increase the incidence of disease. |
| 12 | Disabled Macroautophagy | A condition where the process of autophagy, responsible for clearing out damaged cells and debris, is impaired. |
1. Epigenetic Alternations
Epigenetic alterations refers to changes in the way genes are expressed, without altering the underlying DNA sequence.
According to this research paper; changes in a persons epigenome can be caused by a lots of different factors, including:
- Diet,
- Obesity,
- Physical activity,
- Tobacco smoking,
- Alcohol consumption,
- Environmental pollutants,
- Psychological stress,
- Working on night shifts
To find out more about the epigenome I would recommend this “Epigenomics Fact Sheet” from the National Human Genome Research Institute Home.
2. Loss of Proteostasis
Proteostasis means protein homoeostasis and the loss of proteostasis refers to the disruption of the normal balance of protein synthesis, folding, and degradation in cells.
The loss of proteostasis can occur due to a variety of factors, including both external and endogenous stresses that accumulate during ageing according to this research paper.
3. Deregulated Nutrient Sensing
Deregulated nutrient sensing refers to a situation where the four proteins; IGF-1, mTOR, sirtuins, and AMPK contribute to aging vs help contribute to longevity.
It is thought that turning down the sensing of IGF-1 and mTOR helps to promote longevity and that turning up the sensing of sirtuins and AMPK helps longevity.
Deregulation of nutrient sensing is often associated with metabolic disorders and can contribute to the aging process.
4. Mitochondrial Dysfunction
Mitochondrial dysfunction refers to a condition in which the mitochondria, the organelles responsible for producing energy in cells, do not function properly. This can lead to a variety of symptoms and health problems, including fatigue, muscle weakness, and neurological disorders.
Mitochondrial dysfunction can be caused by a variety of factors, including genetic mutations, exposure to toxins, and chronic diseases such as diabetes and cancer. It can also be a side effect of certain medications.
5. Cellular Senescence
Cellular senescence is a state of permanent cell cycle arrest that cells enter as a response to various types of stress, such as DNA damage, telomere shortening, and oncogenic signaling.
Senescent cells cease to divide and can acquire a distinctive secretory phenotype, which can lead to the accumulation of senescent cells within tissues and contribute to aging and age-related diseases.
They also secrete a variety of inflammatory factors, called the senescence-associated secretory phenotype (SASP) that can promote the development of cancer and other age-related diseases.
According to this research paper changes in a persons cellular senescence can be caused by a lots of different factors, including:
- Oxidative stress
- Telomere damage/shortening
- DNA damage
- Mitochondrial dysfunction
- Chromatin disruption
- Inflammation
- Epigenetic dysregulation
- Oncogene activation
This is why some take senolytics like quercetin supplements.
6. Stem Cell Exhaustion
Stem cell exhaustion refers to the loss of the ability of stem cells to divide and differentiate into various cell types, leading to a decline in their regenerative potential.
Stem cell exhaustion can lead to tissue damage and dysfunction, and is thought to contribute to a range of age-related conditions.
Changes in a persons stem cell exhaustion can be caused by a lots of different factors intrinsic and extrinsic cellular factors, including:
- Aging tissues
- Chronic disease
- Exposure to certain toxins or radiation
7. Altered Intercellular Communication
Altered intercellular communication refers to changes in the way cells communicate with each other, which can have a wide range of effects on the body.
Examples of altered intercellular communication include:
- Changes in signaling pathways
- Changes in the expression of receptors or other molecules that mediate communication between cells
- Changes in the physical interactions between cells
Altered intercellular communication can contribute to the development of a variety of disease.
8. Genomic Instability
Genomic instability refers to a variety of genetic changes that occur in a cell’s DNA. These genetic changes can include mutations, chromosomal abnormalities, and changes in the amount of DNA present in a cell.
Genomic instability can be caused by a variety of factors, including:
- Exposure to radiation or certain chemicals
- Errors in DNA replication
- Defects in DNA repair mechanisms
9. Telomere Attrition
Telomere attrition is the process whereby the terminal caps of the chromosomes become shorter due to reasons.
As cells divide and replicate, the telomeres get shorter, and eventually the cells will no longer be able to divide.
According to this research paper, changes in a persons telomere length can be caused by a lots of different factors, including:
- Smoking
- Poor diet
- Sedentary lifestyle
- Poor stress management
Telomere attrition is thought to play a role in the aging and in the development of certain age-related diseases.
10. Dysbiosis
Dysbiosis is a condition of microbial imbalance caused by an overgrowth of “bad” bacteria inside the gut, associated with potential negative outcomes such as the incorrect production of essential metabolites or even the genesis of harmful metabolites.
Dysbiosis has been reported to be implicated in the development of several disorders, such as obesity, diabetes, chronic fatigue syndrome, intestinal bowel syndrome, cancer, autoimmune diseases, depression, anxiety, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and other neuropsychiatric disorders.
11. Chronic Inflammation
The occurrence of inflammation increases with aging and is also called “inflammaging”.
Chronic inflammation is a persistent inflammatory response that can lead to tissue damage and increase the incidence of disease like arteriosclerosis, neuroinflammation, osteoarthritis, intervertebral discal degeneration and cancer.
12. Disabled Macroautophagy
Disabled macroautophagy is a condition where the process of autophagy, which is responsible for clearing out damaged cells and debris, is impaired. This can lead to the accumulation of damaged cells and debris, which can contribute to chronic inflammation and other health problems.
As we age, the process of autophagy, which is responsible for cleaning up cellular waste, becomes less efficient. This leads to an increase in both intracellular and extracellular waste, including the buildup of malfunctioning organelles and misshaped proteins. Additionally, the body’s ability to eliminate pathogens decreases, and inflammation levels rise.
Gary Kirwan
Founder and Host of BioHackers Lab Podcast
Been interested in biohacking concepts and products since first testing what it is like drinking butter in my coffee years ago. My ultimate goal is healthy aging through exercise, diet, social interaction and psychology.
Sources
- López-Otín et al. 2013. The Hallmarks of Aging.
- López-Otín et al. 2023. Hallmarks of aging: An expanding universe.
- Schmauck-Medina et al. New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary.
- Alegría-Torres et al. 2011. Epigenetics and lifestyle.
- National Human Genome Research Institute – Epigenomics Fact Sheet.
- Dodig et al. 2019. Hallmarks of senescence and aging.
- Oh et al. 2014. Stem cell aging: mechanisms, regulators and therapeutic opportunities.
- Starkweather et al. 2014. An integrative review of factors associated with telomere length and implications for biobehavioral research.
- Shammas M. A. 2011. Telomeres, lifestyle, cancer, and aging.
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