Why are we getting old?
For references to scientific papers, see the original article.
One of the earliest theories of aging is the theory of damage accumulation, proposed by August Weisman in 1882. Cells and organisms are complex systems consisting of many complex interconnected components. But these complex systems are quite fragile and wear out due to the gradual accumulation of damage in trillions of body cells. Thus, the body cannot fully recover, this leads to aging and age-related diseases.
Free radicals
One of the versions of the theory of damage accumulation, called the theory of free radicals, was first formulated by Rebecca Gershman and Daniel Gilbert in 1954 and was developed in 1956 by the American chemist Denham Harman.
Free radicals are natural byproducts of respiration and metabolism, and over time they accumulate in the body. Harman suggested that since cell damage and the number of free radicals increase with age, it is possible that free radicals are the cause of these damages. Harman studied reactive oxygen species (ROS) in depth. They accumulate in the mitochondria as they convert nutrients into energy for cell functioning.
It has been found that ROS can attack DNA, proteins and lipids, altering their properties and functions. Experiments have shown that increasing the production of ROS in yeast, worms and fruit flies shortens their life.
Harman's theory of aging dominated from the 1990s until the early 2000s. But then the results of several studies began to contradict the theory. When the genes of antioxidants (substances that destroy free radicals) were knocked out in animals such as salamanders and mice, this did not affect the lifespan of the organism in any way.
To explain the contradictory results, scientists have suggested that ROS may act as a signal for other defense mechanisms. Or the location of ROS in different cell organelles can lead to different results. While this version is still being discussed, the theory of free radicals may give way to other theories of aging. But with so many studies linking ROS and mitochondria to aging and age-related diseases, there are still grounds for further research.
The evolutionary hypothesis of the development of diseases
Before continuing the description of various theories of aging, attention should be paid to evolutionary biology.
As you know, genes control the production of proteins that form, among other things, the physical characteristics of the body – the so-called phenotype. They can change as a result of mutation. Each person carries many mutations in their genes. Most of these mutations do not affect the body, but some have negative or positive consequences.
Evolution and natural selection imply the preservation and inheritance of genes (or gene mutations) that provide an advantage for the survival of the organism. If a gene mutation leads to undesirable consequences, it is likely that it will be eliminated during evolution.
Many diseases have a genetic basis, that is, they are caused by genetic mutations. So why do "bad" mutations still exist and are not eliminated by natural selection?
In 1957, the American evolutionary biologist George Williams offered an answer. According to his hypothesis of antagonistic pleiotropy, the same gene mutation can lead to both beneficial and harmful characteristics. And if the good outweighs the bad, the mutation is not eliminated.
For example, mutations that cause Huntington's disease improve fertility and reduce the risk of cancer; mutations that cause sickle cell anemia protect against malaria; mutations associated with cystic fibrosis also improve fertility. These are just a few examples out of many.
Some mutations are useful at an early age – they contribute to embryonic development and the birth of children – and become harmful later in life. If they are good for survival and production of the next generation, this may explain their preservation. The hypothesis may also explain the persistence of serious diseases, many of which are common in old age.
But can Williams' theory explain aging? What if genes and proteins that are useful when a person is young later become the main cause of aging? And if so, what proteins are we talking about?
Hyperfunction theory
Mikhail Blagosklonny, professor at the Roswell Park Institute of Oncology, Buffalo, New York (USA), formulated his version in 2006. He suggested that the cause of aging is proteins (and the genes responsible for their synthesis), whose role is to transmit signals to cells about the availability of nutrients. Some of these proteins are enzymes that catalyze chemical reactions in the body. Among them is the enzyme TOR.
When TOR is active, it promotes cell growth. This is necessary at an early age for development and puberty. But in later life, TOR is not needed in such a high concentration. It has been proven that TOR hyperfunction (hyperactivity) is associated with many diseases, including cancer.
If TOR and other genes are the cause of aging, how are they related to damage or to ROS? It has been shown that TOR hyperfunction accelerates cell growth and at the same time weakens defense mechanisms, including the synthesis of antioxidants. This means that the damage can now be considered as a result of hyperfunction of some genes – not the main cause of aging, but its result.
A new theory based on the hypothesis of antagonistic pleiotropy is called the theory of hyperfunction of aging.
The price you have to pay?
Researchers are testing the theory of hyperfunction, and so far the results confirm it. And while these advances explain the root causes of aging and offer ways to combat age-related diseases, they also demonstrate the complexity of the aging process. As evidence accumulates, it becomes clear that aging itself is closely related to gestation, birth, growth and puberty. Who knows, maybe aging is the price that organisms have to pay for survival as a species.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of The Conversation: Why we age – new theories gaining ground.