The fear of getting older

When we are children we look forward to the day of our birthday. That day is own, friends and family give us presents and we blow the candles hoping that all our wishes will fulfil. Over the years gifts decrease and we value that they remember us. But that special day is linked to the fear of getting older. In this article I will talk about what is aging and its genetics.

INTRODUCTION

Rembrandt Harmensz van Rijn (1606 – 1669) was a Dutch painter and etcher. He is considered one of the greatest painters and printmakers in European art. He liked painting self-portraits (Figure 1). There are a lot of his self-portraits and we can look the course of time in his face and his aging.

Figure 1. Self-portraits by Rembrandt (Source: El Mundo)

We relate the word aging with the verb gain (gain experience, gain weight, gain wrinkles) and the verb lose (lose hair, lose loved ones, lose abilities). But what is aging?

Aging is a process that there is a deterioration of homeostatic mechanisms. Homeostasis is a system in which variables are regulated so that internal conditions remain stable and relatively constant (pH, oxygen pressure…). All organs and systems of our body are part of homeostatic mechanisms.

Then, as we age, in our organism the following occurs: decrease the organic functions, as with the stomach, which works worse and it is more difficult to digest; and it is more difficult to adapt, most old people are more easily dehydrated. All this is linked to a tissue atrophy and decrease cell turnover, since the balance between cells that form and cells that are destroyed is lost with age.

Aging is a physiological process, not a disease, although in this physiological situation there is more pathological events.

AGING vs. SENESCENCE

Sometimes when we talk about aging is easily confused with the term senescence. Aging refers to the whole body, while senescence is the aging process at the cellular and organic part.

When a cell suffer a senescent stimulus occurs an arrest cell cycle and DNA damage. It means that cell stops growing because its DNA is damaged. The diminution of cellular proliferation, for example in bone marrow it can cause anaemia.

Tissue cells can enter senescence due to UV radiation and a series of proteins are generated, activating macrophage recruitment of immune cells. These macrophage cells, as part of the immune system, are responsible for removing other harmful cell to the body. Then they kill senescent cells and leave holes, which are covered by new cells. This is what happens in normal skin.

If this process occurs in an old skin, some senescent cells can not die because there are not enough macrophages. Then the tissue will be thinned by their inability to form new cells.

THE 9 HALLMARKS OF AGING

There are a number of factors, including genetic and epigenetic factors that contribute to aging (Figure 2):

1. Genomic instability: there has to be balance between DNA damage and repair pathways. It has to repair DNA to not have a senescent phenotype in the cell.
2. Telomere attrition: they are the ends of chromosomes and will shorten after each cell division. When they are very short the cell dies.
3. Epigenetic alterations: how environment influences in gene expression.
4. Loss of proteostasis: changes in degradation capacity of proteasome, a complex which eliminates unneeded or damaged proteins.
5. Deregulated nutrients sensing: the elderly do not control well their desire to eat, or they eat too much or they eat very little. They have not a good sensitivity to signals of satiety and appetite. The same applies to the sensation of thirst. The elders never thirst and this can cause dehydration.
6. Mitochondrial dysfunction: mitochondria provide energy for cellular activity.
7. Cellular senescence: cell damage processes occur.
8. Stem cell exhaustion: stem cell formation decreases. In muscle cells there are not new cells to repair muscle fibres and muscle is becoming smaller, causing the person is getting weaker.
9. Altered intercellular communication: different cellular pathways do not work well.

Figure 2. The 9 hallmarks of aging (Source: The Hallmarks of Aging)

You can propose a number of alternatives or interventions in each of the above factors that could lengthen the average life of the organism, but still not have the tools necessary to assess all factors that may be involved in aging, although much has been achieved in recent years.

However, the interpretation of what is pathological and what is not supposed one of the main challenges to solve.

REFERENCES

• F. Rodier, J. J. Campisi. Four faces of cellular senescence. Cell Biol. 2011; 192(4), 547-56
• Daniel Muñoz-Espín, Manuel Serrano. Cellular senescence: from physiology to pathology. Nat. Rev. Molecular Cell Biology 2014; 15, 482-496
• C. López-Otin, M. A. Blasco, L. Partridge, M. Serrano, G. Kroemer. The Hallmarks of Aging. Cell 2013