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Hallmarks of Aging
Hallmarks of aging: The 12 signs of aging
Ageing is an inevitable aspect of human life and now, more than ever, its complex relationship with disease is the focus of scientific and medical debate.
A central area of research is concerned with the “Hallmarks of Aging”. These first identified 9 hallmarks of ageing. In 2023, these were expanded by three – so there are now 12 independent biological processes that are assumed to contribute to the ageing process and explain ageing at a cellular level.
The Hallmarks of Aging have revolutionized aging biology by providing a clear and comprehensive framework for the study of aging. This has led to a more structured approach to studying the complex interactions and processes of ageing and has triggered a wave of research activities that allow us to understand the ageing process in greater depth. Accordingly, the hallmarks of ageing form the basis for the development of individualized longevity strategies to delay age-related diseases, extend healthspan and improve quality of life.
All 12 identified hallmarks of aging are interconnected and influence cellular pathways and functions.
These findings and approaches are currently bringing about a paradigm shift in geriatric research and medicine, with the aim of making ageing a fulfilling and less stressful phase of life.
GENOMIC INSTABILITY
Genomic instability is the first feature of the “Hallmarks of Aging” and describes the increase in mutations and DNA damage with age, which increases the risk of cancer and age-related diseases.
This instability is caused by environmental toxins, radiation and defects in DNA replication and repair. Factors such as lifestyle, diet and exercise also influence genomic instability.
Unrepaired DNA damage leads to mutations and disrupts gene expression and cell function, which increases ageing and the risk of disease.
Efficient DNA repair mechanisms are therefore essential to slow down the ageing process and maintain health in old age.
LONGEVITY TIP: Avoid alcohol and tobacco consumption.
TELOMERE SHORTENING
Telomeres are specialized structures at the ends of chromosomes that act like protective caps to protect the genetic material during cell division. Each time a cell divides, telomeres shorten due to the end-replication problem, as DNA polymerase, the enzyme that replicates DNA, cannot fully copy the chromosome ends. This shortening leads to cell senescence, where cells stop dividing or die, contributing to ageing and tissue degeneration.
Longevity research is currently showing promising possibilities for protecting telomere length. Telomerase, an enzyme, is supposed to reverse this shortening by lengthening telomeres. However, telomerase is inactive in most somatic cells, so that the shortening is not compensated for.
Both genetic and environmental factors can influence telomere length. Genetic predispositions determine the initial telomere length and influence the rate of shortening.
LONGEVITY-TIP: Find an indication of the connection between telomere length and DNA methylation with the bioAge test.
EPIGENETIC CHANGES
Epigenetic modifications are marks “on” (“epi”) the DNA that influence how genes work without changing the DNA sequence itself. These modifications accumulate over time, disrupting regulated gene expression and altering cell function, which contributes to the ageing process. They affect proteins and chemical markers that interact with DNA and influence its structure and accessibility, which can promote or suppress gene activity.
In addition, epigenetic changes are also crucial for disease development, as they can activate or deactivate genes involved in diseases without changing the genetic sequence.
LONGEVITY-TIP: Find out your epigenetic profile with the bioAge test and find out your biological age and other parameters.
LOSS OF PROTEOSTASIS
Proteostasis refers to the cell’s ability to maintain a balance of proteins by controlling their production, folding and degradation. This balance is important for proteins to properly fulfill their roles in the cell. As we age, this system becomes less efficient, causing misfolded and damaged proteins to accumulate.
Several factors contribute to proteostasis becoming less efficient with age. These include damage caused by oxidative stress, which can damage proteins and make them susceptible to misfolding. Inflammation exacerbates this condition by altering the cellular environment. Weaker autophagy, the process of removing defective proteins, also reduces the cell’s ability to remove defective proteins.
LONGEVITY TIP: Encourage the production of heat shock proteins through regular sauna sessions or cold water exposure, as HSPs help to support protein folding and break down damaged proteins.
IMPAIRED MACROAUTOPHAGY
Macroautophagy is an essential cellular cleansing process that maintains homeostasis by degrading and recycling damaged organelles, misfolded proteins and waste products. This mechanism is essential for cell health as it prevents harmful accumulations from impairing cell function. As we age, the efficiency of autophagy decreases, leading to cell damage.
Promoting autophagy is important to maintain cellular health and slow down the ageing process. Studies show that caloric restriction and regular exercise could prolong lifespan in various organisms and improve macroautophagy. These methods promote the activity of autophagosomes, which are responsible for the degradation and recycling of cellular waste.
LONGEVITY TIP: Incorporate foods rich in spermidine, such as wheat germ and soybeans, to support autophagy and promote longevity.
DEREGULATED NUTRIENT SENSITIVITY
As we age, it becomes more difficult for the body to properly perceive and respond to nutrients, which is known as deregulated nutrient perception. These mechanisms balance energy in the body and control growth and development. A key aspect is insulin resistance, where cells become less sensitive to insulin. Insulin lowers blood sugar levels and regulates glucose metabolism.
Changes in the activity of growth hormone and IGF-1 also contribute to deregulated nutrient perception. These signaling pathways are important for cell division and metabolic regulation. As we age, they can become disrupted, leading to unbalanced nutrient distribution.
LONGEVITY TIP: Reduce calorie intake without nutrient deprivation, which has extended lifespan in various model organisms and can improve metabolic health. Intermittent fasting has established itself here as a form of diet that combines well with a modern lifestyle.
MITOCHONDRIAL DYSFUNCTION
Mitochondria are tiny structures in our cells that act as small power plants by generating energy in the form of ATP (adenosine triphosphate). ATP is the main energy store in cells and supplies numerous biological processes with the energy they need, which is crucial for healthy energy metabolism and the ageing process. If mitochondria do not function properly, the risk of diseases such as Alzheimer’s, heart problems and cancer increases.
As cells age, the efficiency of mitochondria decreases, leading to reduced energy production and increased oxidative stress. This stress accelerates the ageing process, promotes DNA mutations and increases the risk of cellular dysfunction and disease.
LONGEVITY TIP: A Mediterranean diet, rich in fish, unsaturated fatty acids such as olive oil and nuts, and fresh fruit and vegetables, promotes mitochondrial health and reduces inflammation.
CELLULAR SENESCENCE
Cellular senescence is a process in which cells stop dividing and become permanently inactive, often triggered by stress factors such as DNA damage or telomere shortening. These “zombie cells” release pro-inflammatory substances, known as senescence-associated secretory phenotype (SASP), which can cause inflammation and tissue damage and, above all, cancer.
While senescence is originally a protective reaction to prevent damaged cells from reproducing, the accumulation of these cells with age leads to impaired tissue function and accelerates the ageing process.
LONGEVITY TIP: Use senolytic substances that can help to specifically break down senescent cells and improve tissue health.
STEM CELL DEPLETION
Stem cells are specialized cells that can self-renew and differentiate into different cell types in the body. They are crucial for tissue repair and maintenance throughout the lifespan. As we age, their regenerative capacity decreases, leading to impaired tissue function and increased susceptibility to age-related diseases such as muscle loss, neurodegeneration and cardiovascular disease.
The causes of stem cell depletion are continuous differentiation due to tissue damage, chronic inflammation, DNA damage and epigenetic changes that impair self-renewal. This decline weakens repair mechanisms and accelerates the ageing process.
LONGEVITY TIP: Engage in endurance sports such as running or cycling as well as strength training to promote cellular regeneration and improve muscle stem cell function.
ALTERED INTERCELLULAR COMMUNICATION
Intercellular communication is the exchange of information and signals between cells, which is essential for the function of tissues and organs. This communication takes place through direct cell contact, signaling molecules such as hormones and growth factors as well as extracellular vesicles.
With age, this communication can be disrupted, resulting in inflammation, tissue dysfunction and reduced regenerative capacity.
Restoring healthy cell communication is therefore important for maintaining tissue integrity and preventing age-related diseases such as cancer, neurodegeneration and chronic inflammation.
LONGEVITY TIP: Encourage regular social contact and activities that have a positive impact on neuronal health and intercellular communication.
CHRONIC INFLAMMATION
Chronic inflammation, also known as inflammaging, is persistent inflammation that promotes age-related diseases such as heart disease, cancer and neurological disorders. It occurs when the body’s immune response becomes unbalanced over the long term, causing tissue damage.
With increasing age, the immune system changes, the function of T-cells and B-cells decreases and the production of pro-inflammatory substances increases.
This inflammation impedes tissue repair, promotes the accumulation of damaged cells and contributes to age-related diseases. They are also associated with cognitive decline, depression and other mental declines in old age.
LONGEVITY TIP: Reduce stress and promote healthy sleep through regular exercise, meditation or mindfulness. Avoid excessive calories and substances such as alcohol and nicotine.
DYSBIOSIS
Dysbiosis, the twelfth hallmark of aging, describes the imbalance in the microbial communities that inhabit the gut, skin and other tissues in the body. This disruption of the microbiota can lead to various negative health consequences, including chronic inflammation, metabolic dysfunction and an increased risk of infectious diseases.
In particular, the imbalance of the gut microbiota occurs more frequently with increasing age, which can result in digestive problems and an impaired immune response.
LONGEVITY-TIP: Make sure you eat a diet rich in fiber and variety and regularly include prebiotic foods such as onions, garlic and bananas to promote healthy gut bacteria.
FAQ
The Hallmarks of Aging concept was introduced in 2013 by an international team of leading scientists, including Carlos López-Otín and Guido Kroemer.
They identified the biological mechanisms that influence ageing in order to create a unified model that makes the complexity of ageing easier to understand and serves as a basis for targeted therapeutic approaches.
These hallmarks are important because they reveal the processes that cause cell and tissue damage and thus promote age-related diseases.
The original nine hallmarks were selected based on the scientific knowledge available at the time. As research progressed, additional mechanisms were discovered that also play a role in the ageing process.
The expansion to twelve reflects new scientific advances, particularly in cell communication and cellular degradation. It is possible that more Hallmarks will be identified in the future as science continues to make new discoveries and the understanding of ageing grows.
The Hallmarks of Aging have served as a guide to develop targeted therapies aimed at specific mechanisms of aging. They have significantly increased innovation in aging research by providing a clear framework for studying and modifying the mechanisms of aging. This has enabled the development of new interventions to slow down ageing and improve health in old age.
All 12 identified hallmarks of aging are closely linked and influence cellular pathways and functions.
For example, genomic instability can lead to mutations and chromosomal rearrangements that affect gene expression and cell function, which in turn can lead to loss of proteostasis and mitochondrial dysfunction. Similarly, telomere shortening can contribute to stem cell exhaustion and cellular senescence, which can lead to altered intercellular communication and chronic inflammation.
In order to improve healthspan, targeted measures can be taken to minimize the negative effects of Hallmarks. A healthy lifestyle with a balanced diet, regular exercise, sufficient sleep and effective stress management is crucial.
These lifestyle choices help to slow down ageing, promote longevity and improve quality of life in old age.
Tests such as the omega-3 test, NAD test, gut flora test and biological age tests can be used to assess specific Hallmarks. Supplements such as omega-3 fatty acids support health by addressing some of the Hallmarks. These tools provide valuable insights and support personalized prevention strategies.
Biological processes lead to cell and tissue damage that impairs bodily function. Hormones are critical as they significantly affect cell function and metabolism. Hormonal balance is important to minimize the negative effects of Hallmarks and promote longevity. Regular exercise and a balanced diet support a healthy hormonal balance.
A detailed blood-based hormone test measures the concentrations of specific hormones in the body, such as cortisol, estrogen or thyroid hormones. The purpose of such a test is to identify imbalances that could potentially accelerate aging or affect health. This test provides valuable information about hormonal status and helps to understand the effects of hormones on the ageing process.
With the results of a hormone test, targeted, personalized interventions can be developed to correct hormonal imbalances. This can be done through lifestyle adjustments, such as diet and exercise, or through medical treatments.