Anti Ageing Theory or more accurately the Theory of ageing and how it may be manipulated in the future, falls in to two categories “Why do we age?” and “How do we age?”
While the effects of ageing are well established there are seven competing theories of the cause of ageing, making it difficult to understand the best way to combat it. Let’s look at the main schools of thought on this complex subject and try to assess the best approach to slowing or stopping the process.
Index of Ageing Theory
The Cross-Linking Glycation Hypothesis of Ageing
The Evolutionary Sensescence Theory of Ageing
The Genome Maintenance Hypothesis of Ageing
The Neuroendocrine Hypothesis of Ageing
The Oxidative Damage/Free Radical Hypothesis of Ageing
The Rate of Living Theory of Ageing
The Replicative Senescence Hypothesis of Ageing
Multiple Ageing Process
Before we push-on to look at the seven theories of ageing there is a general principle to cover first. Within the seven ageing models there is an over riding set of assertions driving the research that a finite number of ageing mechanisms are in play, giving science a better chance of developing anti-ageing strategies. If this assertion turns out to be incorrect and multiple or even hundreds of different biological pathways effect ageing, it’s unlikely any treatment to stop ageing will ever be a reality.
Within this assertion there is also evidence of two main reasons for the ageing process. The first being single-gene mutation, the second more well-known is environmental intervention called caloric restriction.
Single Gene Mutation
The argument for a limited number of ageing factors effecting lifespan has so far been witnessed in roundworms, fruit flies, and mice, in the form of single-gene mutations. Research has highlighted these genes apparently affecting only a few biochemical pathways, stress resistance, regulation of insulin/IGF-1, and energy consumption. This is leading researches to to believe that modifying the ageing process in humans could one day be a reality.
Although this research is heading in the right direction there are problems. So far it has been seen that modified animals inherent defects such as infertility.
Perhaps you have heard the phrase “eat less live longer”? Well, it seems as far as the research goes this in fact is a reality. Using worms, insects, and rodents, caloric restriction in the lab has seen animals given balanced but sparse diets of up to 40% fewer calories as normal extend average lifespans. primate are currently under investigation.
What these studies show is a limited calorie intake limits all age related changes including age related diseases. Unfortunately, this too comes at a cost to rodents as they become thin, cold, stunted, and on occasion sterile.
This is based on observations that as we age our structural molecules, DNS and proteins form inappropriate attachments with each other, forming cross-links.
These cross-links have the affect of decreasing the mobility or elasticity of proteins and other molecules, which subsequently prevents the body’s garbage disposal from working.
Normally, when proteins are unwanted or damaged they will broken down by enzymes known as proteases. Unfortunately, with the presence of cross-linkages the activity of the proteases are interrupted causing damaged and unneeded proteins remain.
The main cause of cross linking is a process called glycosylation or glycation. This is where glucose molecules stick to proteins, thereby transforming them into brown molecules called advanced glycosylation end products, or AGEs. So after AGEs stick to their neighbor the cross-link that forms disables the proteins’ functions.
Research supports cross-linking can contribute to the ageing process as it affects the protein collagen responsible for wrinkling and other age-related dermal changes. Also protein in the eye leading to age-related cataract formation, the walls of arteries or the filtering systems accounting for
atherosclerosis or hardening of the arteries.
Age-related decline in kidney function, the formation of beta-amyloid, and possible links to Alzheimer.
Some research carried out in China and UK suggest that Carnosine can help in the preventing cross-linking of proteins.
This theory is the most widely accepted. Rather than a theory looking for a way evolution might favor aging, this one focuses on the failure of natural selection to affect later life traits. This is where defects are passed on due to the fact Natural selection working through reproduction, but genes and mutations with harmful affects will only appear in later life. Not only this, but predation and accidents dictates more younger individuals reproducing than older ones.
The idea of passing on less than perfect genes is known as the mutation accumulation theory proposed by Peter Medawar 1952. Sometime later George Williams added to the theory calling it “antagonistic pleiotropy” which essentially argues that genes increasing the odds of reproducing in early life can have harmful effects in later life. This is because the negative effects of the gene will not been seen until after reproduction so guaranteed to by passed on.
An example of this in humans would be the damage to the gene responsible for directing damaged cells to stop reproducing or die. this gene prevent cancer in the young but reduces the ability to regenerate cells in later life. The knock on effect then, of editing genes to improve later life could easily effect the health of the younger.
So what does this all mean to us? There has been a lot of study in this area and evidence exist to support the basic premise of evolutionary senescence. The theory at its roots suggests delaying the age of reproduction will delay ageing due to the increased power of natural selection in later life.
Evidence for this are found in the lab work on fruit flies where young flies where prevented from reproducing, only older flies reproducing. The lifespan of the older breeders were extended, with the payoff of being less fertile in early life than normal flies, giving support to antagonistic pleiotropy.
Here we see our body constantly under attack, our DNA being damaged thousands of times a day any changes or mutations to egg or sperm cells will be changes passed on in inheritance. This damage can be caused be environmental factors like toxin, oxidative free radicals, or mistakes in replication.
The changes and mutation in other parts of he body will be be corrected or eliminated but those that survive will accumulate, and cause cells to malfunction, but only effect the individual and never passed on. This is the basis for normal ageing.
Within this model we see the role for mitochondria which create dangerous free radicals as a by product of energy generation. Over time mutations accumulate in the DNA of the mitochondria adding to the decline in their corect functioning.
It’s lucky for us, our bodies are pretty good at making repairs which is why human have longer lives. As time passes thought, things start to change. For example if we look at the DNA in white blood cells we can see 2% to 4% of these cells to be damaged in young adults, while in the elderly this percentage is six times higher. This can directly explain the weakening of the immune system in the elderly.
The neuroendocrine system the system of complicated connections between the brain, nervous system, and endocrine glands, which produces hormones. Part of the system is the hypothalamus at the base of the brain that stimulates and inhibits the pituitary gland, which in turn regulates other glands ovaries, testes, adrenal glands, thyroid.
With age the system becomes less functional leading to high blood pressure, impaired sugar metabolism, and sleep issues. For a long time research on ageing looked closely at neuroendocrinology which is the study of hormones regulated by the brain.
It was thought for some time that later life reduction of hormones like estrogen accompanying the menopause was responsible for aging. There are however, studies as far back as the 1960s that suggest although late-life brings reduced hormone levels, the reduction in hormones can lengthen life.
During normal cell metabolization toxic by products known as Oxidative free radicals are created. As this happens antioxidants within the cells neutralize these dangerous free radicals, but those that escape the process can cause damage to DNA, proteins, and mitochondria by way of cross-linking. Over time the oxidative damage accumulates causing ageing related conditions such as cancer, heart disease, diabetes, and Alzheimer’s disease.
Most study is focused on the effects of free radicals on the mitochondria as 90% of free radicals are produced there making them particularly susceptible to damages. If they are not neutralized by antioxidants fast can cause serious damage to the membranes of mitochondria and to mitochondrial DNA.
While it’s true mitochondria have the ability to repair their DNA this ability declines with age, and the damaged creates a self-perpetuating cycle damaging mitochondrial function resulting in the creation of yet more free radicals. Indeed, too much mitochondrial damage leads to apoptosis or cell suicide.
This theory is the oldest in town, known to the Ancient philosophers who believe in a the quantity theory of “vital substance” whether that was breaths or heartbeats, without which death followed. Enter the 20th century and scientists keep the theory but bolt on an energy consumption limitation to longevity.
The idea of metabolic rate determining lifespan was seen to be consistent with the discovery that free radicals the by product of normal metabolism, can damage cells and contribute to aging over time.
Although some lab work has been carried out with cold-blooded organisms with slow metabolic rates, results have been mixed. Now it’s believed while metabolic rates can affect aging that doesn’t mean that it always does will.
And on the other side of the coin we can see birds typically have a metabolic rate 1.5 to 2.0 times that of mammals of similar size but they live on average about three times longer. The overall results are not thought to hold water for the Rate of Living Theory and overall it has been rejected. The only intervention known to prolong life being caloric restriction without reducing the animal’s metabolic rate.
We now know human human cells derived from fetal, embryonic, or newborn tissue have a limited capacity to reproduce themselves by dividing between 40 and 60 times. Modern science believe the Hayflick Limit as it’s known is related to the length of a cell’s telomeres.
If you like the Telomeres can be looked at as protective caps on the ends of chromosomes. Each time a cell divides, it first doubles its chromosomes so the duplicate has a full set of genetic material, but each time this happens it loses a small amount of the telomeres.
At some point the telomeres reach a limit around the 40 to 60 population doubling and can no longer divide. They have become “senescent”, living but unable to replicate. For scientist this was seen as the reason for ageing, a kind of cellular count down clock but there was an issue. Not all human cells are actively replicating for example Muscles cells of the heart, and Brain cells, and to cap it all, shortening of the Telomere is not universal among all species.
In terms of multiple ageing processes it’s the testing of these hypotheses and the identification of ageing mechanisms that could lead to intervention leading to the slowing or stopping of the ageing process. Research suggests these mechanisms could be limited, giving scientist greater opportunity in developing life changing strategies.
If the idea of limited mechanisms effecting the ageing process is correct, then one likely cause of ageing could be linked to single-gene mutations proved to affect the lifespan of lab animals. This factor also goes hand in hand with already well understood idea of caloric restriction.
In laboratory conditions caloric restriction where a wide range of subjects including insects and rodents, have had their calorie intake reduced to 30% – 40% of “normal” intake, have shown an increase of average lifespan. Already caloric restriction has been seen to slow all age-related changes in mice, including disease, and currently work is being carried out with primates.
But just browsing through this piece we can see some answers formulating form preventing mitochondria damage, to hormone replacement therapy, to using antioxidants, and caloric restriction. We already know this is a complex issue and the best way through it is knowledge so we can make informed decisions about our own health and happiness.
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