Biological clock. What is ageing and how is the age of the body determined?

It is difficult to say whether everyone is interested in how long they will live. Certainly, however, for many people information on their current state of health and biological age would be interesting and perhaps useful. How, then, is biological age assessed? What is ageing? What are the hypotheses about the causes of ageing? And why do we get older at all?

What is old age actually like? Death from old age must be distinguished from death due to illness. An example of a stillbirth may die from an infection because his immune system was no longer able to cope with it. But how long would he live if he had ideal conditions? If it was not exposed to infectious diseases, falls, etc.? To what extent would it allow him to have his own DNA, his cells, his metabolism? That would be real death from old age. It is worth distinguishing the meaning of the notion of immortality - it is more realistic, that is, the cessation of ageing of our DNA, cells and organism - from fantastic immortality, where no atomic weapon is able to kill the alleged lucky one. There are organisms that actually do not seem to age (they are walking very slowly). Such a phenomenon is called negligible aging. Unfortunately, it was not observed in mammals, but only in plants, invertebrates, fish, amphibians and reptiles.

First of all, I would like to tell you a little about aging in general. The causes of this phenomenon are seen among at least a few mechanisms. The most (traditionally) exposed are reactive oxygen species, free radicals, which damage DNA, proteins and cell membranes. They induce mutation, cause inflammation and cell failure (although it is worth knowing that they also perform necessary functions in animal organisms, e.g. signalling and mobilisation). However, free radicals are currently considered by biologists to be only one of the ageing agents, but not the determining factor, as demonstrated by various studies, including mutant rodents with manipulations on free radical concentrations and experiments with antioxidants.

Everyone is probably wondering whether it makes sense to consume additional amounts of antioxidants in the form of special foods or dietary supplements, since free radicals seem to be one of the enemies of youth. The answer is not unambiguous, or in fact it is almost non-existent. Much can depend on the condition of your body. Some people have an increased expression of antioxidant enzymes, such as peroxide dismutase, glutathione peroxidase or haemostatic oxygenase. Besides, our endogenous antioxidants are certainly more important than those that are exogenous and derived from food, and increased intake of the latter may reduce the expression of the former, which is considered rather unfavourable. Therefore, it is not always good to swallow additional antioxidants. There are publications from epidemiological studies showing that there is a correlation between additional intake of vitamin E or beta-carotene and shorter life. The fashion of eating antioxidants - whatever they may be, whenever and whatever they may be - seems to be unjustified in terms of substance.

In the ageing process, telomeres are considered to be the next factor, or rather their degradation. These are the ends of chromosomes, which protect them from damage, joining into "ring" chromosomes and other molecular structural pathologies and dysfunctions. How does it happen that telomeres protect chromosomes? Our distant ancestors had circular DNA, so replication occurred from the first to the last nucleotide. This is still the case today for most of the pro-carnates. However, the eucaronite chromosomes evolved into filamentous structures. Each subsequent replication is therefore associated with the loss of a fine, final fragment of the chromosome. Therefore, something had to be created that would protect the cell against too rapid loss of functional genes after a certain number of replications. So instead of them, the sequences of encoders, not the telomeres, are lost. To illustrate this function easily, the telomeres are usually compared to the ends of the laces, so that they do not break. As we age, our telomeres change, they become shorter. Their regeneration is becoming weaker and weaker (except for cancer cells, where the gene encoding the telomerase, the telomerase correction enzyme, is very expressive). This process is one of the components of aging.

The ageing effect is also attributed to insulin and insulin-like growth factors (known as insulin growth factors (IGF)). This hormone is secreted by the beta islands of the pancreas when we eat. Sugars released from the food during digestion are absorbed and transferred to the bloodstream and further to the cells. So it is an information that the body is in shape, because it has managed to get food. This signal has probably evolved as a symptom of the possibility of procreation, and from the body's dispositional hypothesis it follows that the body must balance its expenditure on body maintenance and reproduction. So when he gets the message that there is an opportunity to reproduce, more energy is devoted to expressing the genes important in sexual behaviour, etc. This is done at the expense of energy used, for example, to synthesize antioxidant enzymes or repair proteins in somatic cells. Moreover, genes that are useful and supportive at an early age can later in life negatively affect health and vitality. Natural selection thus promotes greater chances of survival in youth, at the expense of a long life. This concept is dressed in a set of theorems, in the form of an antagonistic thesis of pleiotropy.

Research shows that the rate of aging is significantly influenced by the number of calories consumed. Reduced food intake extends the life of laboratory rodents significantly, and similar observations have been made in humans based on epidemiological analyses. This is probably related to a lower risk of obesity, cardiovascular diseases, inflammation and cancer. Perhaps this phenomenon is somehow connected with the insulin mechanism described above. It is known, however, that calorific restrictions may have a beneficial effect on the regulation and activity of sirtuins, "youth proteins" (also stimulated by resweratrol).

The accumulation of genetic mutations due to free radicals or unfixed errors occurring during replication causes the genetic system to produce defective RNA and proteins, which means that the body is unable to function normally, defend itself against infections and further attacks of free radicals. Proteostasis is disturbed, i.e. the proper formation, functioning and regulation of protein activity. The cancer process may also start. The cells commit apoptosis (programmed death) and as a result the heart loses its efficiency after years of work. The accumulation of mutations in DNA is therefore another element of the aging process. In addition, the presence of precursor cells, which are the stem cells for a given tissue type, is important. These are cells that reproduce the population of a given organ. Their exhaustion, disturbances or damage to DNA also affect ageing.

Also the activity of mitochondria becomes dysfunctional over time due to mutations occurring in mtDNA. The aging process of our mitochondria can be slowed down to some extent by exercise, which is simple and obvious. When we take care of regular physical activity, mitochondria are "more likely" to be shared. Therefore, new and new ones are being created. If we multiply them at a younger age, when they are still healthy, with a small number of mutations, then for the future we have more desired mitochondria. Such a mechanism (though not only) explains the positive impact of physical activity on life expectancy.

There is also an epigenetic biological clock. It is based on DNA methylation in the regions of CpG islands, i.e. sequences rich in repeated cytosineguanine (dinucleotides). For clarification, DNA methylation is the process of incorporation into nucleotides, usually cytosine (sometimes also adenine) of an alkyl group (CH3), also known as methyl. Chromosome fragments, where methylation is high, are more strongly packed (condensed), and this limits access to them for transcription factors. As a result, the expression of the mutilated genes is reduced or completely restricted. The DNA methylation pattern can be epigenetically inherited. It also changes with age, and it is from this property that the biological epigenetic clock draws its inspiration.

Nowadays, we are able to estimate the relative biological age of the organism on the basis of parameters such as DNA damage, telomer length or the degree of dinucleotide methylation in the CpG islands. Ageing has evolved over millions of years. Answers to the questions posed at the beginning of the article therefore require reference to evolutionary biology. This is a good example of how important it can be in medicine or dietetics. This theme also reminds us that it is not necessarily right to follow the fashion of antioxidants as elixirs of youth thoughtlessly. It is worth following further scientific advances in discovering more precisely what ageing is like, what its causes are and how it can be prevented.