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Ageing Process and Evolution
Dr. Chitta Ranjan Santra
Reader, Department of Chemistry, Netaji Nagar Day College, Kolkata
The only certainties in life, said Benjamin Franklin are death and taxes. Don't expect either to disappear anytime soon. As we grow older, our hair turns grey, our bones grow thin and among other changes, our telomers shrink. The telemors, the tips of the chromosomes, do more than simply becoming markers to the passage of time, they harbor answers to the fundamental mechanisms of ageing and cancer. Now researchers propose how these molecular clocks may ultimately count down the final days of a cell's reproductive life.
Ageing refers to the time-sequential deterioration that occurs in most animals including weakness, increased susceptibility to disease and adverse environmental conditions, loss of mobility and agility, and age-related physiological changes. Ageing is usually understood to include reductions in reproductive capacity. It may be assumed that ageing includes changes in reproductive capacity including behavioral patterns such as “reproductive vigor” or strength of the urge to mate.
Some scientists use the term ‘senescence' to indicate the deteriorating effects of aging as opposed to the simple passage of time. Ageing means the deteriorating effects. A non-ageing animal does not age but does “get older” and has increasing “calendar age”. Ageing is now not a fundamental, totally unalterable fact of life. Ageing is actually like a universal but potentially highly treatable genetic disease.
Knowledge on the evolution of ageing aims to explain why almost all living things weaken and die with age. There is not yet agreement in the scientific community on a single answer. Historically, ageing was first likened to ‘wear and tear': our bodies get weak for the same reason that a knife gets dull or metal rusts. However, this idea was discredited at the onset of the second law of thermodynamics which states that entropy (disorder) must increase inevitably within a closed system, but living beings are not closed systems. In fact, it is a defining feature of life that we take in free energy from the environment and unload our entropy as waste. Living systems routinely repair themselves, and, in fact, can build themselves up from seed. There is no thermodynamic necessity for ‘senescence'.
Why do we age?
The importance of this question is determined by your preconception of the answer. If you think ageing is “an inescapable biological reality”, or “an inevitable fact of life”, or otherwise caused by a process that is so fundamental, so immutable and so central to the process of life that no alteration is possible, then determining the cause is very academic and of little importance. At the bottom line, there is nothing that can be done about the root cause of ageing. Spending much effort or money on finding the cause is foolish. Geriatrics research should be confined to the amelioration of symptoms and treatment of specific age-related conditions such as Alzheimer's disease.
If, on the other hand, you think ageing is caused by something more like a genetic disease, something along the lines of hemophilia, then the answer to the question “why do we age?” is critically important. It will lead us in the right directions to finding major treatments that will eventually have a monumental beneficial effect on people's lives. A treatment for ageing could result in delaying or ameliorating “age-related” diseases that now kill more than eighty percent of the people who die in the developed world and substantially extend the length and quality of countless lives. It can be shown that ageing is not inevitable, is not inescapable and that anti-ageing research if aggressively conducted could result within a reasonable time in major new treatments for ageing as well as in many age-related diseases.
Most medical advances have been the result of experimentation. Ageing, because it is a relatively long-term process, is a difficult subject for experimentation. An experiment to determine if a medication is effective in relieving pain, or increases kidney function, or suppresses a certain infectious organism, could be performed in a matter of days or weeks. A solution through medication to increases longevity in animals or humans could take years, decades, or even multiple decades to evolve.
The relatively gradual and mild effects of ageing also tend to be masked by other processes. As an illustration, researchers have been able to determine the functions of various glands by removing a gland from a laboratory animal and observing the results. However, removal of most glands is rather immediately fatal. If a gland had an effect on the ageing process, observation of that effect would be masked by the gland's more critical functions. Until recently, experimental approaches have been unable to shed much light on the causes of aging. As a consequence, scientific theories of ageing are primarily the result of logical analyses of the functional, externally observable, characteristics of various organisms. You can readily picture the difficulties associated with this approach. Imagine trying to deduce the existence of, much less the detailed functioning of the endocrine system, or other largely internal system, merely by observing how animals live and die. It is difficult or impossible to prove such a logical theory without experimentation, which remains difficult. Various theories of aging, some dating from the 1800s are still debated.
A group of theorists, using more recent data has developed theories indicating that the fundamental causes of ageing may actually be much more ‘treatable' than predicted by the traditional theories. In addition to producing their own theories, these theorists have discovered many logical flaws and inconsistencies in the traditional theories. The potential health implications are staggering since most of the people who currently die in developed countries die of “age-related” diseases and conditions such as cancer, heart disease and stroke. Scientific theories differ from the new theories mainly in their response to “ Darwin 's dilemma”. {It was that observed animal characteristics regarding ageing and longevity did not fit the rules set forth by Darwin for natural selection. Contemporary scientists cited ageing and longevity as a demonstration that Darwin's theory of natural selection was incorrect using the following logic: Since longevity was of value in increasing and survival time and breeding opportunity of any organism, would not natural selection (if true) result in ever-increasing longevity? Wouldn't ageing, since it was obviously adverse to fitness be “selected out” by the process of natural selection? In other words, Darwin 's theory predicts that animals and humans should not age}. The chronological development of Darwin 's theory of evolution, the traditional ageing theories, the various discoveries that relate to ageing and the new theories are important. Darwin 's response was that he believed that longevity was a characteristic determined by natural selection, that is, an evolved characteristic or adaptation. Evolution is a change in the gene pool of a population over time. Evolution is a process that results inheritable changes in a population spread over many generations. “In the broadest sense, evolution is merely change and so is all-pervasive; galaxies, languages and political systems all evolve. Biological evolution is change in the properties of populations of organisms that transcend the lifetime of a single individual. The ontogeny of an individual is not considered evolution; individual organisms do not evolve. The changes in populations that are considered evolutionary are those that are inheritable via the genetic material from one generation to the next. Biological evolution may be slight or substantial. It embraces everything from slight changes in the proportion of different alleles within a population (such as those determining blood types) to the successive alterations that led from the earliest proto-organism to snails, bees, giraffes, and dandelions. The most common action of natural selection is to remove unfit variants as they arise via mutation, (natural selection: differential reproductive success of genotypes). In other words, natural selection usually prevents new alleles from increasing in frequency. This led a famous evolutionist, George Williams, to say, “Evolution proceeds in spite of natural selection.”
Welsmann's Theory of Programmed Death: Weismann suggested that “programmed death” was a genetically programmed, evolved characteristic, (an adaptation) and that this characteristic had evolved through natural selection because it conveyed a benefit to the species even though it had a negative effect on individual fitness. ‘Weismann's thought was that by removing older members of the population, programmed death provided more resources (such as food and habitat) for younger members) The younger animals were presumably one or more generations more evolved than older animals. Programmed death therefore shifted resources from less evolved to more evolved animals and therefore improved the species' ability to evolve, that is, it improved its ability to adapt to changes in its external world through natural selection. Weisman's theory had a major benefit: it explained the inter-species differences in life span. If aging was an evolved characteristic, then we would expect the sort of major species-specific variations that we observe in other evolved characteristics. Weismann's theory violated an implicit requirement of the theory of natural selection, namely, that in order to be selected by a trait ha to be expressed in such a way that it affects survival. Natural selection works by the differential in life span between animals that have a beneficial characteristic and those that do not. If almost all the animals died of other causes before the age at which “programmed death” was activated, then it could not have affected survival and thereby natural selection.
Accumulation of Damage Theories: One obvious way out of Darwin 's dilemma would be to declare that ageing was not an evolved adaptive characteristic but was instead a result of some fundamental property of life, or some fundamental physical limitation or at least some process other than natural selection. As years passed, many such theories appeared.
Nuclear background radiation (or other disrupting influence) could cause cumulative, gradually increasing, damage to DNA or cell structure or some other critical function, causing ageing. Some poisonous by products of life processes could accumulate, gradually causing deterioration. There could be some fundamental limitation on the number of times cells can divide. Mechanical devices inevitably wear out eventually. Would this not also apply to living organisms? Some essential and irreplaceable ingredient could be gradually used up. The laws of entropy say that everything goes from an ordered to a less ordered state as time passes. Could not ageing be an example of entropy and therefore a fundamental property of life?
People who are familiar with human ageing but not as familiar with ageing in other species often subscribe to one of these theories. Most biologists became eventually determined that these genetic accumulations of damage theories were not credible in light of observed characteristics of animals especially the differences between species. The arguments regarding wearing out do not really apply to living things. Fingernails, hair and claws grow to replace worn items. Teeth are replaced in many animals. Damaged tissue heals (to some extent, which varies from species to species). Some creatures can replace a lost limb.
The other main problem with the accumulation of damage theories is that they do not explain why ageing so resembles an evolved characteristic. Specifically, how is it that some species have dramatically different life spans than other, similar, species? Why would the accumulation of damage be so different in a crow than a parrot? Why would a mouse wear out 100 times faster than a human? Living organisms do share many common fundamental properties of life. All organisms on Earth have extensive common chemistry and biology. However, the differences between species suggest that observed life spans are not the result of any fundamental limitation or any generic process that affects different species equally. Most biologists no longer believe in the accumulation of damage theories.
The Evolution of Senescence: Since the results of senescence, the loss of physiological function and eventually death, do not have any evident fitness advantages, then why have they evolved? Ever since biologists have determined that does definitively lead to a decline in physiological function, the question as to why this occurs has become the most pressing problem to solve. For without a comprehensive understanding of the how and the why phenomena, such as a gradual decline in physiological function occurs, very little can be done to alter the rate of the decline. Although there is not yet a single explanation of the evolution of senescence, there are currently two main theories.
Passive “Mutation Accumulation” theory: Harmful genetic mutations that manifest in physiological decline but do not act until after the peak reproductive time (later in Life) cannot be selected against and therefore will naturally accumulate in a population.
Active “Antagonistic Pleiotropy theory”: Late acting harmful genes may be actively selected for if they have benefits during earlier life stages. In both of these theories, senescence occurs as the inevitable result of the declining force of natural selection over time.
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