Why do people age?

2023-11-09

At present, the pursuit of immortality seems to be out of reach, and people are turning to hoping to live healthier and longer. In order to achieve this goal, we first need to answer a question - why do people age?

The earliest explanation for aging at the cellular level was the telomere hypothesis. Telomeres are special regions at both ends of chromosomes that have the function of protecting chromosomes. Every time a cell divides, the chromosomes are replicated. Studies have found that after each replication, the telomeres of the chromosomes will shorten a little. When the telomeres are shortened to a certain extent, the chromosomes will stop replicating, thereby preventing the mother cell from dividing to produce new daughter cells. When there is no replenishment of young cells, the body gradually ages. The telomere hypothesis was partially confirmed in the experiment of cloning Dolly the sheep. However, other cloning studies in recent years have found that the lifespan of cloned animals is not directly related to the youth of the selected cells. It can be seen that this hypothesis has certain limitations.

Epigenetics now provides a better explanation of cell longevity. Epigenetics refers to the regulation of biological traits by affecting gene expression through methylation or acetylation of bases when the gene sequence remains unchanged. Simply put, the genome is like the hardware of a computer, and epigenetics is the software that tells the genome when to turn it on and when to turn it off. For example, except for germ cells, the genes of other cells in the human body are exactly the same, but the morphology and function of brain cells and pancreatic cells are completely different. This is because the genes are methylated at different times and at different sites.

However, genes are susceptible to damage during expression and lead to breakage. At this point, the nucleosomes (the basic organizational units of chromatin, also known as chromatin granules) made up of DNA (deoxyribonucleic acid) and proteins become relaxed, and the repair proteins in the cell move to the break to join the two pieces of DNA for gene repair. There are trillions of cells in the human body, and thousands of these genetic breaks and repair events occur every minute. As the number of repairs increases, some repair proteins may be biased, leading to gene misexpression: genes that should be expressed are turned off, but genes that should be turned off remain in working state. This causes cells to lose their original functions, causing the body to age.

To prove this, biologist David Sinclair selected two twin mice with the same genotype for the experiment. He used an enzyme to speed up the DNA fragmentation of one of the mice at a factor of three. After three weeks of experimentation, he found that the mice were showing signs of aging, such as slow movement, organ failure and dementia. Finally, Sinclair sequenced the DNA of the two mice and found that their DNA was identical, without any genetic mutations. This is a direct demonstration of the correlation between aging and epigenetics.