It has been accepted that we all are born to die. When I visited my beloved mother in 2006, a few weeks prior to her death, she asked me “are there anything in the medical science to reverse my serious medical condition?” Then my mother was only 83 years, compared to 175 years of longevity for Abraham in Old Testament. I was always intrigued why the longevity of human being reduced since the biblical times. However, when I looked into the longevity of human beings I found that, it was only 24 years in 1786, and after 100 years it doubled to 48 years. Currently the oldest person on record lived to be 122 years old.
To understand the intricate mechanism of ageing process, one needs to refresh their understanding of structural components of a cell. Mainly they are, nucleus, mitochondria and cell membrane. The nucleus is the the master control of a cell which contains genes, which are collections of DNA. These are arranged into chromosomes. Mitochondria is the powerhouses of the cell which also contains collections of DNA, involving in the production of high energy compound called Adenosine Tri Phosphate (ATP).
Telomeres are keys in determining ageing process. They are located at both ends of each chromosome. Each time chromosome replicates a small amount of the DNA at both ends are lost by an uncertain mechanism, thereby shortening the telomere. At birth human telomeres are 10000 base pairs long, but by 100 years of age this has been reduced to about 5000 base pairs. Telomerase, is an enzyme, capable of arresting or reversing this shortening process. Reduction in telomeres are involved in the development of cancer and other diseases. Therefore, shortening of telomeres are a deciding factor in ageing process.
Mitochondrial DNA (mtDNA) gets mutations more often and faster than the DNA in the nucleus. One of the reasons for mutation is due to the presence of Reactive Oxygen Species (ROS) or FREE RADICALS in the mitochondria. Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. When mitochondria makes ATP, it creates ROS or free radicals which damages mtDNA. If someone eats less food, fewer ROS created, which in turn results fewer mutations, thereby increasing longevity. Vegetables, cereals and fresh fruits are anti oxidants which reduce free radicals in the mitochondria. However increased free radicals, damage the function of mitochondria and then it becomes dysfunctional. Reduced energy formation leads to ageing and ultimately to death.
Research into ageing process has been going on for many years through experimentation on animals. It has been found that most animals and birds die after a few years of sexual maturity. But certain reptiles like tortoise live for over 150 years. The lifespan of Bowhead whales is 200 years which is longer than any other mammals. It has been reported that Greenland sharks live for between 300 and 500 years and are the longest living vertebrate. They take life very slowly, moving at an average of 0.76 mph. They do not achieve sexual maturity until they are 100-150 years old.
Factors boosting longevity which have been invented
by scientists in Harvard University, US are exercise, less food, stress,
hunger and taking metformin. Recent study on metformin has found that
its mitochondrial action inhibits Complex 1 of the respiratory chain,
and thereby metformin increases ATP production. Metformin also increases
hunger and stress due to lactic acid accumulation. Physical activity
reduces many major mortality risk factors including arterial
hypertension, diabetes mellitus type 2, dyslipidaemia, coronary heart
disease, stroke, and cancer. All the above diseases are decreased by 30%
to 35% in physically active as compared to inactive subjects. It also
increases energy level and metabolism. It is recommended that150 minutes
of moderate exercise or 75 minutes of vigorous exercise per week yields
approximately 3.4 extra years to one's life. Both help to reverse the
ageing process.
Epigenome has a role to play in the research into
ageing process. Epigenome is a network of chemical compounds surrounding
DNA that modify the genome without altering the DNA sequences and have a
role in determining which genes are active in a particular cell.
Epigenome is capable of activating a specific gene. Scientists construct
epigenetic clocks by selecting sets of DNA-methylation sites across the
genome. As the ageing process is associated with altered epigenetic
mechanisms of gene regulation, such as DNA methylation, histone
modification and chromatin remodelling. DNA methylation causes a crucial
modification to the genome that is involved in regulating many cellular
processes. These processes include chromosome structure and stability,
DNA transcription, and embryonic development.
Stem cell therapy is a
form of regenerative medicine designed to repair damaged cells within
the body by reducing inflammation and modulating the immune system.
Induced Pluripotent Stem Cell( IPSC) have particular potential in the
field of ageing biology. This technology has been used in age related
macular degeneration of retina, which can lead to blindness. IPSC,
involving stem cells would benefit patients suffering from Parkinson’s
disease, arthritis and even to make new teeth to replace those lost to
decay over our lifetimes. These diseases are the scourge of old age.
Nicotinamide Adenine Dinucleotide(NAD+) is a coenzyme that plays a
critical role in supporting many biological processes within the body.
These are entirely natural compound found in our body. Mitochondrial
activity of creating energy is facilitated by NAD+. Various food sources
also contain this compound in minuscule amount. Increased NAD+ levels
stimulate energy metabolism. Vitamin B3 or Niacin s a precursor of NAD+
and helps to reverse ageing process. Nowadays, NAD+ supplements are
available in the market.
Every person has an epigenetic age in addition
to chronologic age. If one’s epigenetic age is higher, than chronologic
one, one may accelerate ageing process and die early. Epigenetics is the
collective name for a set of chemical flags stuck to DNA. Smoking, lack
of exercise and excessive food intake also expedite the process of
ageing.
Previously drinking coffee, and playing brain games were thought to be reducing ageing process.Ageing should not be accepted as a natural process.Ageing is an unfortunate consequence of reality. Now the horizon of reversing
ageing is becoming brighter and more realistic. Like conquering space, it is time to conquer ageing.
Dr.C.J.George FRCS
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