Living systems have the intrinsic ability to respond, to counteract and to adapt to the external and internal sources of disturbance. This is what makes them different from the inorganic and non-living systems. Traditionally, the biological age of organisms was considered to be related to the underlying homeostasis inside the bodies of the organisms. It was then found out the homeostasis is not the right term to describe the living state and ageing as the term homeodynamics encompasses the fact that, unlike machines, the internal milieu of biological systems is not permanently fixed, is not at equilibrium, and is a dynamic regulation and interaction among various levels of organization. The property of homeodynamics of the living systems is based on a wide range of maintenance and repair systems (MARS) at all levels of organization.
MARS refers to maintenance and repair systems which basically are the mechanisms or activities associated with the routine care and upkeep of our internal structures and biological functions in order to keep them at a steady state.Some of the main MARS are: nuclear and mitochondrial DNA repair; anti-oxidative enzymes and free radical scavengers; degradation of damaged DNA, RNA, proteins and other organelles; apoptosis; detoxification of harmful chemicals and metabolites; Immune responses; wound healing and tissue regeneration, and other higher order processes such as thermal regulation, Neuro-endocrine balance and circadian rhythms. All these processes involve hundreds of survival assurance genes whose products and their interactions give rise to a “homeodynamic space”, which is the ultimate determinant of an individual’s chance and ability to survive and maintain a health. At the molecular level, the theories of the mechanisms of aging are mostly centered on the occurrence and accumulation of molecular damage.
WHAT AFTER ALL IS AGEING?
Aging is the result of imperfect maintenance and repair systems that allow a progressive shrinkage of the homeodynamic space of an individual.
BIOGERONTOLOGY
The study of the biological foundation of aging and age-related disorders is known as biogerontology. In evolutionary and biological terms, the phenomenon and process of ageing are well understood, and a conceptual framework has been constructed within which general principles of ageing and longevity can be stated. The phenotype of ageing, in terms of increasing loss of physical function and fitness, is best visible during the period of survival after a species' essential lifetime (ELS) has been defined by evolution. At all levels, from the complete body to the molecule, the aging phenotype is very heterogeneous and individualistic. Most importantly, the aging process and progression are not determined by any specific gerontogenes.
The foundation of biogerontology is built on three pillars:
- Ageing is defined as a progressive loss of physical function and fitness that culminates in death of an individual in the continuum of life at the end of a species' natural lifespan, referred to as the 'essential lifespan' (ELS) .
- There is no strict programme or gerontogenes that have evolved specifically for the purpose of producing an individual's ageing and death.
- Variable species, individuals within a species, organs and tissues within an organism, cell types within a tissue, subcellular compartments within a cell type, and macromolecules within a cell all have different ageing process, rate, and phenotypes.
Even there is a limitation to the number of times a cell can divide in its lifespan. Here comes the concept of Hayflick limit. It states that a normal human cell can only replicate and divide forty to sixty times before it cannot divide anymore, and will break down by programmed cell death or apoptosis.
Biological aging is a meta-phenomenon that is emergent, epigenetic, and not Controlled by a single mechanism or central regulator. Individually, no tissue, organ, or system gets functionally exhausted until the death of a very old organism; the quality and longevity of an individual's life is determined by the dynamic interaction and interdependence at all biological levels.
WHAT CHANGES LEAD TO AGEING AND DEATH OF AN ORGANISM?
In Darwinian terminology, biological ageing is thought to occur mostly during the period of survival beyond the natural or essential lifespan (ELS). Organisms are able to attain ELS due to their genetically set longevity, which ensures that maintenance and repair systems are in place . The steady build-up of molecular damage produced by environmental and metabolically generated free radicals, spontaneous errors in biochemical reactions and mobilisation of nutritional components characterises ageing at the molecular level. There is significant degradation of the maintenance and repair systems as a result the organism becomes older and there is molecular heterogeneity, cellular malfunction, lower stress tolerance, illnesses, and eventually death.
WHY WE THINK WE CAN REVERSE THE AGEING PROCESS?
The Non-genetic, epigenetic, and environmental factors all play a role in determining an individual's lifetime, with them accounting for more than 75% of the variance. This also means that ageing, health span, and lifespan are not fixed and may be altered.
History of attempts made to reverse ageing
This is not the first attempt to reverse ageing. Humans have been trying to find a solution to it for a very long time. Ayurveda is one such medical practice whose history is more than 5 thousand years old and the method used to prevent aging in Ayurveda is called Rasayana.
5 thousand years ago, King Gilgamesh of Egypt had designed a complete programme based on China's medical practice to overcome ageing. About 2 thousand years ago, the famous Egyptian queen Cleopatra used Donkey's milk to stay young. This might sound weird but this milk is being used in huge quantities for making beauty products.
Recent research and scope of future research to reverse ageing
Israeli scientists have carried out research that will help fight aging. The research was conducted on 35 volunteers who were more than 64 years of age. The volunteers were provided with clean oxygen for 90 minutes a day, five days a week in a pressurised chamber. The experiment continued for three months and the end result was appalling.
The scientists claim that ageing in all 35 volunteers got arrested which means the researchers in a period of just three months successfully carried out the process of reverse ageing. The scientists were successful in curbing two age-enhancing processes: the telomere and malfunctioning cells in the body.
A telomere is the last end of a Chromosome that protects it from damage during replication. Every time there is a replication the telomere takes a hit and shortens. By each passing day, they become shorter in length. And when they become very short the chromosomes are unable to replicate and the ageing process begins.
The scientists have not only limited the damage to the telomere but have also been successful in decreasing the number of inactivated cells by Oxygen Therapy.
Bio Gerontologists are beginning to narrow down the potential ageing pathways, including insulin/IGF-1 growth axis, m-TOR activity, and stress resistance, which could be amenable to manipulation .But there is also evidence that those and other metabolic pathways can be effectively modulated by life-style alterations, such as intermittent food restriction, exercise and nutritional and pharmacological interventions.
The discovery novel hormetins as modulators of aging and longevity is a promising area of research offering numerous opportunities in the aesthetic, healthcare and food-industry.
Another experimental ageing interventional approach being tested is that of so-called gene therapy. One of the earlier experimental studies demonstrated that an induced mutation in a single gene increased the lifespan of the nematode C. elegans . Since then hundreds of putative gerontogenes or longevity genes have been reported in C. elegans, Drosophila and rodents, which when mutated result in the extension of average and maximum lifespan of the organism. It is important to realize that in almost all such cases, longevity extension had occurred when one or multiple interventions resulted in the reduction or total inhibition of the activity of one or more genes.
CHALLENGES
One major challenge still is to translate the information gathered from studies performed on experimental-model systems of insects, nematodes, rodents and others to human beings.
Another challenge for bio gerontologists trying to develop effective means of ageing intervention is to come out of the reductionistic mode of doing experiments. The history of ageing intervention research has shown that taking this or that single compound of natural or synthetic origin, force-feeding it to some experimental model system, and analysing one or few molecular targets has, so far, not lead to any really useful practical interventions for human beings. The three pillars of health – food, physical activity, and mental and social engagement – require a change in the way bio gerontologists design and perform experiments. And most importantly, bio gerontologists also need to be clear as to what is the ultimate aim of such research: Is it to eliminate aging and death forever, and should they do that?
CONCLUSION
As the current data suggests, a quite fascinating number of attempts have been made to reverse ageing but according to the well-understood principles of ageing and longevity, occurrence of biological ageing is certainly inevitable owing to the imperfections of survival mechanisms. Ageing must be approached as a stage in life history of an individual, which is served best by biomedical, technological and social interventions, which could diminish the severity of age-related frailty, along with a possible extension of health-span.
