THE 9 HALLMARKS OF AGING

A Landmark Paper 

In 2013 a team of researchers attempted to identify and categorized the cellular and molecular hallmarks of aging.

They broke down the causes of aging into 9 distinct scientific "hallmarks" and explained how these interact with each other to drive the onset of age-related diseases

Today there are multiple available therapies, and many more being researched, that use this framework to directly intervene against the aging process.

READ THE FULL SCIENTIFIC ARTICLE

Published in final edited form as: 

Cell. 2013 Jun 6; 153(6): 1194–1217.

9 HALLMARKS

Genomic Instability

Impact on Aging:

Genomic instability is a fancy way of describing accumulation of DNA damage. As cells age, their chromosomes become less stable. As repair mechanisms fail to correct DNA damage, mutations accumulate and lead to aging and disease. Genomic instability is a key hallmark of aging.

Currently Available Beneficial Therapies:

NAD+ : Necessary for DNA repair, and decline in NAD+ leads to Oxidative Stress accumulation; as such NAD+ has shown a lot of promise in animal models and in invitro studies

Telomere Attrition

Impact on Aging:

As cells divide, the telomere ends of chromosomes get shorter. Eventually, the enzyme that adds telomeric repeat sequences, telomerase, gets silenced and the telomeres are too short for cells to divide.

Available Beneficial Therapies:

NONE

Epigenetic Alteration

Impact on Aging:

Epigenetic Alteration refers to damage that alters the interpretation of the genome, and not the sequence of the DNA. This happens as cells are exposed to environmental factors, and such changes accumulate over time. This has been correlated with the decline observed in aging cells.

Available Beneficial Therapies:

NONE

Loss of Proteostasis

Impact on Aging:

As cells age, environmental stresses add up and mechanisms responsible for maintaining proper protein composition (autophagy) start to decline. Proteins lose their stability, autophagic processes start to fail, and misfolded proteins accumulate.

Available Beneficial Therapies:

NONE

Deregulated Nutrient Sensing

Impact on Aging:

Metabolic activities can put stress on our cells. Too much activity, and changes in nutrient availability and composition cause cells to age faster. Metabolism and its byproducts, over time, damage cells via oxidative stress, ER stress, calcium signaling, and mitochondrial dysfunction. Therefore, organisms depend on multiple nutrient sensing pathways to make sure that the body takes in just the right amount of nutrition – not too much, not too little.

Available Beneficial Therapies:

Metformin : Studies have shown that metformin indirectly inhibits mTOR and activates longevity pathways beneficial to improved Nutrient Sensing.

Mitochondrial Dysfunction

Impact on Aging:

As cells age, their mitochondria start to lose their integrity due to the build-up of oxidative stress. Compromised mitochondrial function leads to a number of events, such as increased apoptosis induction, that correlate with aging.

Available Beneficial Therapies:

NAD+ : In aged mice, NAD+ boosting restored mitochondrial function to that of young mice. See Youtube video

Cellular Senescence

Impact on Aging:

Cellular senescence is the point at which our cells stop dividing and growing due to damage or lack of necessary components. As cells age, they lose their ability to actively divide and start to undergo senescence.

Available Beneficial Therapies:

NAD+ levels decline in aged human tissues, resulting in changes in oxidative stress and cellular metabolism, suggesting link between NAD+ metabolism and senescence.

Additionally, prescription drug Dasatanib has shown very positive senolitic benefits. AgelessRx is working on launching a patient-funded Dasatanib senolitic trial in the second half of 2020

Stem Cell Exhaustion

Impact on Aging:

As we age, our stem cells eventually lose their ability to divide. Furthermore, we are unable to replace the stem cells that have migrated, differentiated, or died. As a result, we show outward symbols of aging, such as grey hair.

Available Beneficial Therapies:

NONE

Altered Intercellular Communication

Impact on Aging:

Cells, as they age, show an increase in self-preserving signals that result in damage elsewhere. Altered intercellular communication with aging contributes to decline in tissue health.

Available Beneficial Therapies:

NONE

RESEARCH IN PROGRESS

While the currently available age prevention (and potentially age reversing) treatments available to the public are limited to products like metformin and NAD+ infusions, this is rapidly changing. 

 

There are many more promising therapies and technologies under development.

A few that are further along include:

  • GAIM

  • DTL201/DTL151

  • Sarconeos

  • SkQ1

  • Elamipretide

  • GS010

  • UBX0101

  • Fisetin

  • MSC Therapy

  • Wnt pathway

  • HSC Favtors

Learn more here

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