Reviewed by the BioHackers Lab Team | Last updated: January 30, 2023

There are nine 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.

A smiling woman aging well
Image: Canva

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.

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.

What Are the Nine Hallmarks of Aging?

The 9 hallmarks of aging according to the research paper published in the Journal, Cell, are:

  1. Epigenetic Alternations
  2. Loss of Proteostasis
  3. Deregulated Nutrient Sensing
  4. Mitochondrial Dysfunction
  5. Cellular Senescence
  6. Stem Cell Exhaustion
  7. Altered Intercellular Communication
  8. Genomic Instability
  9. Telomere Attrition

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

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.

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