Gene Therapy Against Aging Found to be Successful

The first successful gene therapy in a human increases telomere length and lowers biological age by 20 years.

First time use of gene therapy to increase telomere length in a human
Biological reduction in the age of white blood cells
Delays age related illnesses

Gene therapy 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:

Telomerase
Myostatin

Telomerase

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.

Telomere Shortening And Ageing
Telomeres are cap- like structures at chromosome ends that play an important role in ageing and in the initiation and progression of various diseases.

‘Anti-aging solutions based on telomere length could soon be the elixir of youth.’

Functions 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 factors like:

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.

Dyskeratosis Congenita: 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, scientist 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.

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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.

Having More Children Slows Down the Process of Aging in Women
A study by Simon Fraser University researchers suggests that the number of children born to a woman influences the rate at which her body ages.

Elizabeth 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.
Corresponding with 20 years reduction in biological age of white blood cells.

The data from this study was successfully validated by two organizations:

Biogerontology Research Foundation which is a charity based in the UK.
Healthy Life Extension Company (HEALS) a non-profit organization based in Brussels.

Further tests will be conducted 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.

Nobel Medicine Prize Awarded to Trio for Research on Aging
Elizabeth Blackburn, Carol Greider and Jack Szostak of the United States have won the Nobel Medicine Prize for fingering a key molecular switch in cellular ageing.

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.

References:

Bruno 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
Telomere Extension Turns Back Aging Clock in Cultured Human Cells
https://med.stanford.edu/news/all-news/2015/01/telomere-extension-turns-back-aging-clock-in-cultured-cells.html
http://www.yourgenome.org/facts/what-is-a-telomere
Telomeres, Lifestyle, Cancer and Aging
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370421/
http://learn.genetics.utah.edu/content/chromosomes/telomeres/

Source-Medindia