- First time use of gene therapy to increase telomere length in a
- Biological reduction in the age of white blood cells
- Delays age related illnesses
that increases the telomere length of the chromosome is found to slow aging in cultured cells. The 45-year-old CEO of BioViva, Elizabeth Parrish, risked her life on that theory when she opted for a trial gene therapy that was aimed at controlling the loss in mass of muscles and the lowered telomere length noticed in aging cells.
The risk that Ms. Parrish took paved the way for the first successful gene therapy that was aimed at reversing aging. The two aspects of aging
that were identified and focused on in this trial were:
Telomeres are repeats of
nucleotides that are present at the ends of the DNA strand to protect it. The
same sequences of DNA are repeated many times, which is TTAGGG for humans. They
consist of nearly 15,000 base pairs and are 3000 nucleotides in length, but
they start to shorten over time and as the age of the individual increases.
‘Anti-aging solutions based on telomere length could soon be the elixir of youth.’
of the Telomeres:
- The chromosomes are organized into the cells with the help of telomeres.
- They act as the 'plastic cover over the tip of shoelaces', preventing the chromosomes from opening up.
- They protect chromosomes by not allowing them to stick to each other.
- There is a loss of 25 to 200 base pairs during every cell division. In the absence of telomeres, there would have been considerable loss of important information if parts of the DNA are lost. However, due to the presence of telomeres, only parts of the telomeres and not the chromosomes are lost.
- They protect the genome from nucleolytic degradation.
When telomere length is shortened beyond a certain limit, it leads to:
- Senescence or
apoptosis of the cell
- Age-related diseases
- Health defects
- Tumor formation
Studies have shown that certain dietary changes and lifestyle changes aid in lowering the extent of telomere loss during cell division. The negative correlation between telomerase length and aging
is noticed in normal somatic cells while telomerase enzyme helps in adding telomere units to the ends of the chromosome in:
- Hematopoietic cells
- Germline cells
- Stem cells
- Other cells that undergo rapid division
A human loses 24.4 to
27.7 base pairs every year and the extent of telomere loss depends on certain
- Age- Telomeres progressively shorten as we age.
- Stress - Stress results in an increased secretion of glucocorticoid hormones that suppress antioxidants in the body, increasing the level of oxidative stress and DNA damage. This leads to a shortening of telomere length, affecting health and longevity.
- Genetic Makeup, Presence of Genetic Diseases - Certain genetic diseases can lead to shorter telomere length resulting in premature aging and early heart conditions.
- Epi-genetic Makeup - Epi-genetic factors like DNA methylation also play a role in telomere length.
- Body Weight - Obesity leads to an increase in oxidative stress in the body as well as instability in the genome. Obesity leads to increased loss of telomere length, approximately 8.8 years.
- Exercise - Regular exercise aids in burning fats that are undesirable or harmful and also helps in removing the waste from the body. This improves oxidative stress in the body and also controls the shortening of the telomere.
- Environment - Pollution plays a significant role in telomere length shortening. Studies have shown that traffic policemen who are exposed to vehicle pollution have lower telomere length when compared with normal people of their age.
- Diet plays an important role in telomere length. Fiber rich foods are found to favor telomere length while a diet rich in polyunsaturated fatty acids like linoleic acid has a negative effect on telomere length. Omega 3 fatty acids reduce the shortening of these telomeres.
- Smoking - Studies have shown that smoking cigarettes reduces a further 5 base pairs. If an individual smokes a pack of cigarettes every day for 40 years, in telomere years, it is 7.4 years.
- Women who bear more children show longer telomere length.
Telomeres are a reflection of the rate of aging of an individual, which is far more indicative of impending disease conditions and associated diseases than the age of an individual. When the telomere length is lowered or below a certain critical limit, it increases the chances for certain health conditions like coronary heart disease, diabetes, myocardial infarction, heart failure and increased risk for cancer. Head and neck cancer, lung, renal cell, breast cancer
, bladder and gastrointestinal cancers could develop due to shortened telomere lengths.
: This is a genetic disorder that is characterized by the lower production of telomerase RNA gene that is associated with shorter telomere lengths. This disease condition is associated with premature graying of hair, bone marrow failure, increased susceptibility to infections, increased risk of cancer and premature death.
Gene Therapy to Increase the Length of Telomeres in Mice
The importance of the
length of telomeres in aging and well-being has encouraged numerous researches
into increasing its length, thereby delaying aging.
In a study published in EMBO Molecular Science
Marie A. Blasco and colleagues showed how increasing telomere lengths can
improve the lifespan and health of older mice.
The scientists introduced the telomerase
gene into the mice using an adeno-associated virus vector and telomeres were
added to the back of chromosomes. The normal lifespan of the mice was 150
weeks; scientists in this experiment took older mice to understand the effect
of the telomere increase on life span.
They found that mice
which were one-year-old had a 25% increase in lifespan while mice which were 2 years old
had a 13% increase in lifespan. The benefits of telomere extension in these
mice were not solely restricted to the number of additional days of life but
also extended to the health of the mice. These mice showed an improvement in
metabolic functions, stronger bones, enhanced ability to recognize objects and
improved balance and motor skills.
The study on mice showed promise that gene therapy involving an increase in telomere length can extend lifespan
and also the quality of life as it helps in improving certain health factors.
Parrish said, "Current therapeutics offer only
marginal benefits for people suffering from diseases of aging. Additionally,
lifestyle modification has limited impact for treating these diseases. Advances
in biotechnology is the best solution, and if these results are anywhere near
accurate, we've made history."
Ms. Parrish received two gene therapies from the company that she
co-founded. Her telomere length that was taken in 2015 showed that it was
shorter than the telomere lengths for people of her age, indicating that she
would probably suffer from age-related
illnesses earlier than her counterparts. However, post gene therapy, when her
telomere length was studied in 2016, it was found that there was a:
- 6.71kb to 7.33 kb
increase in white blood telomere length.
with 20 years reduction in biological age of white blood cells.
The data from this study
was successfully validated by two organizations:
Research Foundation which is a charity based in the UK.
Life Extension Company (HEALS) a non-profit organization based in
Further tests will be
including the myostatin enzyme on Ms.
Parrish, called patient zero, and the implications on other tissues and organ
systems will be studied for greater understanding. Critics blamed Ms.
Parrish for trying the therapy on herself, for trying to usurp the limelight. However,
Ms. Parrish has denied the claims and has stated that she felt it was
totally safe and therefore took it upon herself.
BioViva is one among
many anti-aging start-ups that have been founded based on the premise that 'aging'
could be just like another disease with a medicine available for cure. This
could change the way the world perceives aging and take humans
a step closer to immortality.
There are other prominent anti-aging start-ups like Human Longevity Inc started by Craig Venter, which has received funds of over 70 million dollars and Google's Calico, which has a 1.5 billion dollar funding. The elixir of youth may soon become a reality as these companies work towards anti-aging solutions
through gene therapy.
Bernardes de Jesus, Elsa Vera, Kerstin Schneeberger, Agueda M Tejera, Eduard
Ayuso, Fatima Bosch, Maria A. Blasco "Telomerase gene therapy in adult and old
mice delays aging and increases longevity without increasing cancer" EMBO
Molecular Medicine. doi: 10.1002/emmm.201200245
Extension Turns Back Aging Clock in Cultured Human Cells
Lifestyle, Cancer and Aging