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What Shortening Telomeres Say About Your Life Expectancy

Hallmarks of Aging: Telomere Attrition (1 of 9)

The “9 Hallmarks of Aging” are a new framework for looking at the aging process first proposed by longevity science guru Aubrey de Grey. The hallmarks are 9 cellular processes that have been identified as contributors to the aging, and eventual dysfunction, of cells. 

The identification of these 9 processes is now propelling longevity science to develop age-delaying and age-reversing therapeutics. We think that to maximize your longevity strategy, it is important to have a basic understanding of these 9 hallmarks of aging. That’s why we created this series. 

The first hallmark of aging, Genomic Instability, can be found here.

Below, we provide an overview of Hallmark #2: Telomere Attrition.


Hallmark #2: Telomere Attrition

Accumulation of DNA damage (Hallmark #1), appears to affect the genome randomly, but there are certain chromosomal regions that are particularly susceptible to age-related deterioration. One such region is the telomeres, found at the ends of chromosomes.

The telomeres are DNA sequences that protect the ends of chromosomes from early deterioration or fusion with neighboring chromosomes. Telomeres are often compared to the plastic caps at the ends of our shoelaces, protecting the lace from fraying. 

It is clear that as we age, the telomeres at the end our DNA molecules tend to erode and get shorter. As fragments of telomeres are lost in each replication, the DNA of the cell is left increasingly unprotected. 

DNA damage at telomeres causes a persistent type of damage that leads to other negative cellular effects, including senescence and/or apoptosis. Ultimately, this involves the loss of the regenerative capacity of different tissues.

There are two explanations for why telomeres are particularly susceptible to deterioration:


Telomerase Exhaustion

The first explanation for the deterioration of telomeres, is the exhaustion of an enzyme called telomerase. This enzyme is essential for the effective replication of the terminal ends of DNA molecules. In mammals, telomerase is not expressed bymost cells (stem cells are the exception), which leads to the progressive and cumulative loss of telomere-protective DNA sequences from chromosome ends.

Telomerase depletion has also been linked with the development of other disease, such as pulmonary fibrosis, dyskeratosis congenita, and aplastic anemia, each involving the loss of the regenerative capacity of different cells. 

Telomere structure Normal human lymphocyte DNA

Telomere structure. 

Normalhuman lymphocyte.Telomeresare shown in yellow. 

DNA of chromosomes is shown in blue. 

Aubert, G., & Lansdorp, P. M. (2008). Telomeres and aging. Physiological reviews, 88(2), 557-579.

Shelterins

The second reason telomeres get damaged has to do with shelterins. These are proteins that bind telomeres to the rest of the DNA strand. Their obOne effect of shelterins is that they make telomeres invisible to the DNA repair mechanism in the cell. So, when DNA damage does occur at the telomere, it goes undetected.

When telomeres become too short, shelterin proteins can’t properly bind to them. Telomeres are then no longer protected by the shelterin proteins and induce DNA damage signals, eventually leading to genomic instability, senescence, or cell death. 

Shelterin protein complex DNA Damage Machinery

Shelterin protein complex. Shelterin proteins bind to the repeated TTAGGG telomere sequences and shield them from the DNA damage machinery. 

Shay, J. W. (2018). Telomeres and aging. Current Opinion in Cell Biology, 52, 1-7.

New therapies are on the way

Telomere attrition has drawn much attention from start-up and research groups looking to develop therapeutic treatments to delay and reverse aging. 

Results from animal models have validated the effect of telomere repletion. Evidence indicates that aging can be successfully delayed in mice by telomerase activation without increasing the incidence of cancer. This activation can be done in different ways, for instance through pharmacological agents like  TA-65 supplementation or  gene therapy

In humans, recent meta-analyses have indicated a strong relation between short telomeres and mortality risk, particularly at younger ages.

This has motivated many research teams to develop therapeutics for humans. The  Life Extension Advocacy Foundation, highlights these three efforts as the most promising anti-aging therapies in development:

  • Telocyte: focuses on the development of telomerase therapy to treat Alzheimer's disease. Their therapy seeks to restore telomeres in target cells. Currently awaiting a start on human clinical trials.
  • CNIO The National Center for Oncological Research in Spain is working to develop new ways to prevent, diagnose, and treat cancer. The CNIO has developed a telomerase therapy able to reverse aplastic anemia and reverse fibrosis in mouse models, among several other achievements. Their work on the progressive shortening of telomeres associated with organism aging can be found  here.
  • AgeX Therapeutics: The focus of this company is applying biotechnology to age-related diseases for damaged tissue regeneration in humans. According to the LEA Foundation, AgeX has already identified key pathways that could potentially unlock the regenerative potential in adults. Currently in preclinical in vivo stages. 

What you can do 

While these innovative solutions get to market, there are many things that we can do to help protect our telomeres. 

According to  this scientific review, “[b]etter choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan.”

These lifestyle strategies are ones we consistently emphasize here at Nowgevity as well:

  • Exercise: Studies indicate that exercise might delay human biological aging. While chronic stress  accelerates cell aging and people suffering from it generally have shorter telomeres, there is some  evidence that vigorous exercise helps protect that effect by buffering its effect with telomere length.
  • Sleep: Sleep duration is positively  associated with telomere length, suggesting that shortening of telomeres  might reflect mechanisms through which short sleep contributes to pathological conditions.
  • Nutrition:There is  evidence that various nutrients influence telomere length through several cellular functions like inflammation, oxidative stress, DNA integrity, DNA methylation, and activity of telomerase. Some nutrients which are positively associated with reduced attrition of telomere length include  Omega-3 fatty acids, Polyphenols, Curcumin, and Vitamin B9, B12, B6, vitamin A, D, C, and E, as well as several other minerals. 

Additional resources:

The Hallmarks of Aging: Telomere Attrition | LifeXtenShow

CNIO Maria Blasco - Role of Telomeres in Aging

The 9 Hallmarks of aging - Cell

Telomeres and aging- Cell biology


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