Top 10 Root Causes of Aging 2022

What Causes Aging?

What happens in your body that leads to the problems of aging? Latest research uncovered 10 key mechanisms.

Anti-Aging Supplements David Sinclair Takes

1. Mitochondrial Dysfunction

  • Mitochondria are the power plants of our cells. They produce the energy that our cells need to stay alive and function properly.
  • Cells contain hundreds to thousands of mitochondria on average.
  • The older we get, the more our mitochondria become damaged and dysfunctional.
  • Mitochondria become damaged by various mechanisms during our lifetime, such as mutations in their DNA when they divide, by free radicals, and due to epigenetic changes.
  • When mitochondria are damaged, cells don’t have enough energy to properly function and maintain themselves. Also, damaged mitochondria send signals to the cell, further disrupting proper cellular functioning. This leads to aging.
  • Various natural substances can improve mitochondrial health, such as Nicotinamide Mononucleotide (NMN), malate, alpha-ketoglutarate, glycine, glucosamine, vitamin C, and pterostilbene

2. Senescent Cells

  • During aging, more and more senescent cells arise in our tissues.
  • Senescent cells are cells that have become damaged, but that resist dying. They keep staying alive, and secrete substances that damage surrounding, still healthy cells.
  • Senescent cells undermine the proper functioning of tissues, especially when they accumulate above a certain threshold, secreting substances that are proinflammatory, damage the tissues, and accelerate aging.
  • Specific substances can destroy senescent cells. Such substances are called “senolytics”. Examples of natural senolytics are fisetin and quercetin.

3. Loss of Proteostasis

  • Proteins are the building blocks and workhorses or our cells: they build up our cells and carry out most of their functions.
  • Proteins are continuously broken down, recycled and rebuilt, a finely tuned process called protein homeostasis or “proteostasis”.
  • However, this process is not perfect, and during our lifetime more and more proteins start to linger around, starting to accumulate, forming protein heaps or clumps, both inside and outside cells.
  • These protein heaps or clumps eventually grow so big that they hinder the proper functioning of cells. Too much protein accumulation can lead to “proteotoxicity” and even the demise of the cell.
  • Protein accumulation is one of the reasons why cells become dysfunctional during aging or in fact why they age.
  • Specific natural substances can slow down protein accumulation, such as glycine, pterostilbene, lithium and glucosamine.

4. Altered Intercellular Communication

  • When we get older, increasingly higher levels of deleterious substances can be found in our bloodstream and cellular fluids.
  • Examples of such substances are proinflammatory factors and many other proteins, peptides, metabolites, and hormones that damage our cells and accelerate aging.
  • Probably many of the most damaging circulating substances are the ones that promote a continuous state of low-grade, systemic aging-related state inflammation, also called “inflammaging”.
  • The increase of these inflammatory factors is caused by various mechanisms, including senescent cells, a dysregulated microbiome, a leaky gut, the aging immune system, chronic pathogens like viruses, mitochondrially-derived proinflammatory substances, and so on.
  • Specific natural substances can reduce this pro-aging cellular milieu, for example by reducing inflammaging (low-grade aging-related inflammation).

5. Epigenetic Alterations

  • The epigenome determines which genes are switched on or off.
  • The epigenome enables far more precise regulation of cellular functioning than the genome (our genes or DNA).
  • The older we get, the more the epigenome becomes dysregulated: beneficial genes are turned off that should be turned on, and deleterious genes are turned on that should be switched off.
  • Many other changes happen to the epigenome, undermining the cells’ ability to function properly, contributing to the aging process.
  • Reprogramming the epigenome has shown to extend lifespan in organisms, and can even partially reverse aging.
  • Specific substances can beneficially impact the epigenome, such as Nicotinamide Mononucleotide (NMN), glycine, fisetin, alpha-ketoglutarate, vitamin C and lithium.

6. Genomic Instability

  • As decades pass, our DNA becomes more and more damaged.
  • DNA contains the instructions to build proteins, which carry out most of the functions in our cells. Proteins also build up our cells.
  • The more DNA is damaged, the less cells can carry out their functions properly.
  • Too much DNA damage also activates various responses of the cell, leading to further damage, or to the rise of senescent cells, which are cells with too much DNA damage that secrete harmful substances.

7. Telomere Shortening

  • Telomeres are the short caps at the ends of our DNA strands that prevent the DNA from unraveling.
  • You can compare telomeres with the caps at the ends of shoelaces which prevent them from unraveling.
  • With each cell division telomeres become shorter.
  • After many cell divisions, the telomeres have become so short that they cannot protect the DNA anymore, which starts to get damaged.
  • Telomeres not only shorten, but also get more and more damaged during aging, which also leads to cellular stress and DNA instability.
  • Telomere length is not strongly correlated with lifespan. However, the speed at which telomeres shorten is strongly correlated with lifespan.
  • Cancer cells have the ability to continuously lengthen their telomeres, making them “immortal” in the sense they can keep dividing without their telomeres becoming too short, which would lead to cell death.
  • This led many scientists to believe that lengthening telomeres increases the risk of cancer.
  • However, studies have shown that lengthening telomeres does not contribute to a higher cancer risk. In fact, longer telomeres can protect against cancer, especially given short telomeres are associated with genetic instability, which increases the risk of cancer.

8. Deregulated Nutrient Sensing

  • During aging, important metabolic pathways become more and more dysregulated.
  • These pathways regulate how our cells respond to nutrition.
  • Examples of these pathways are receptors in the cells that gauge amino acid and carbohydrate levels, or that measure intracellular energy levels.
  • The more these nutrient sensing pathways are activated by nutrients like amino acids or glucose, the faster we age.
  • This is because an overabundance of nutrients shifts cells into the “lazy” modus, so that they repair and mainstem themselves less well, which accelerates aging.
  • On the other hand, a scarcity of nutrients, as happens during fasting or by reducing nutrient intake, puts cells into a maintenance and repair modus, which slows down aging.
  • The western diet with an overabundance of fast sugars, animal proteins and unhealthy fats leads to an overactivation of these nutrient-sensing pathways, and accelerates aging.
  • Specific natural substances can inhibit these nutrient-sensing pathways, enabling the cells to repair, maintain, and protect themselves better.

9. Stem Cell Exhaustion

  • Stem cells give rise to the cells that build up our tissues. For example, mesenchymal stem cells generate bone cells, fat cells and fibrous tissue cells. Liver stem cells build liver cells. Hematopoietic stem cells produce white blood cells and red blood cells.
  • During aging, stem cells become dysfunctional or die off.
  • This leads to our tissues being less replenished and maintained.
  • Stem cells decline because of epigenetic changes, DNA damage, telomere shortening, protein accumulation, mitochondrial dysfunction and other aging mechanisms. These mechanisms damage and age the stem cells.
  • Specific natural substances can improve stem cell health such as Nicotinamide Mononucleotide (NMN).

10. Crosslinking and Advanced Glycation End Products (AGEs)

  • Crosslinks are connections or links between proteins that make up our tissues.
  • Linking proteins together makes the tissues more stiff and rigid.
  • This rigidity hardens blood vessels, lung tissue and cartilage, contributing to various aging-related diseases, like hypertension, pulmonary problems and osteoarthritis.
  • During aging, more and more crosslinks form in our tissues. Many of these crosslinks are made of sugar.
  • Consuming a diet with little sugars can slow down the formation of crosslinks.



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