Although the cell is only a dozen microns in size, there are many factors affecting aging in this "square inch". Mitochondria, endoplasmic reticulum and lysosomes in organelles, histones regulating cell transcription and DNA methylation in nucleus will affect cell aging. —— Liu Lin, Professor, School of life sciences, Nankai University Throughout the ages, the pace of human exploration of immortality has never stopped. However, it is still difficult for mankind to reverse the natural law of birth, age and death. However, with the continuous development of modern science, we are gradually discovering the essence of human aging, and the methods of delaying aging seem to have traces to follow. Some Pacific rockfish can live more than 200 years, which is one of the oldest vertebrates known, while some Pacific rockfish can only live more than 10 years. In a recent article published in the journal Science, researchers compared the genomes of nearly two-thirds of rock fish species living along the Pacific coast, revealing some genetic differences that make their lifespans very different. The understanding of aging begins with cells The aging we can see with the naked eye starts with wrinkles in the skin, flowers in the eyes, and more and more "small problems" in the physical examination every year. The secret that makes our body produce this series of changes is hidden in every small cell in our body. "Cell aging is the root cause of body aging. Aging generally starts from the tiny gene level." Professor Liu Lin, School of life sciences, Nankai University, said that although cells are only more than ten microns in size, there are many factors affecting aging in this "square inch". Mitochondria, endoplasmic reticulum and lysosomes in organelles, histones regulating cell transcription and DNA methylation in nucleus will affect cell aging. Cell senescence is closely related to chromosome telomere. Telomeres are like a "protective cap at the end of shoelaces" for chromosomes. Due to the lack of the role of telomerase, the protective telomeres will become shorter and shorter with each DNA replication of cells, and finally the telomere length will be shortened to prevent DNA damage, resulting in continuous mutation or loss of genomic DNA, accelerating human aging and causing many diseases, Therefore, telomeres are also known as the "molecular clock of life". Mitochondria, the main organelle involved in cell metabolism, is also an important organelle regulating cell aging. "Mitochondria produce very important molecules in the process of energy metabolism and participate in normal activities such as gene regulation and transcription." Liu Lin introduced that mitochondrial energy metabolism is abnormal, and it will produce many oxides such as free radical ions in the respiratory chain. If the antioxidant reductase in our body can not remove these oxides in time, they will "refuse to recognize each other". Oxidation includes many structures of mitochondria itself, and will enter the nucleus and affect genomic DNA. For example, DNA and telomere are easy to be oxidized and damaged, which is also a recognized theory about mitochondrial aging. At the same time, telomere shortening also affects mitochondria. Liu Lin explained that when telomeres are shortened and cannot function normally, they will activate some molecules, affect the function of mitochondria, and reduce the function of mitochondria through molecular regulation. "The better the function of mitochondria, the less oxides, the more stable telomeres and the longer life span, and vice versa." Mitochondria will oxidize the cell membrane and intimal system. Therefore, the endoplasmic reticulum in organelles will also undergo degenerative changes due to cell aging. Calcium is an important regulatory substance that helps mitochondria and endoplasmic reticulum communicate with each other. There are pores between mitochondria and endoplasmic reticulum. Usually, extracellular calcium ions enter the cell and need to be transported to the cytoplasm by cell membrane, and then flow into the endoplasmic reticulum. The endoplasmic reticulum contains specific ion regulatory channels and is very close to mitochondria. Therefore, when the endoplasmic reticulum releases part of calcium ions into the cytoplasm to regulate cell metabolism, some of them go to mitochondria to regulate mitochondrial function. If there is a defect in the function of endoplasmic reticulum or mitochondria, too much calcium ions will be released into the cytoplasm, resulting in cell death. Conversely, excessive calcium loss leads to calcium deficiency, which will also affect the normal work of cells. Abnormal calcium release and calcium deficiency can lead to cell aging. Liu Lin said that only by maintaining a certain calcium ion level, maintaining the calcium oscillation of cells, and the free calcium ions in the cytoplasm can be effectively stored in organelles and released during work, can the normal work of cells be ensured. This regulation can effectively delay cell aging. Various paths to find and decode the aging code Human beings have been trying to find and decode the password of aging from various paths. Recently, scientists have made new progress in the field of aging research. For example, Liu Guanghui's team from the Institute of zoology of the Chinese Academy of Sciences found a molecular switch to "keep cells young", which can slow down the pace of cell aging by resetting the epigenetic clock of aging. "The new human aging promoting gene kat7 found by Liu Guanghui's team is a gene that regulates epigenetic inheritance. When this switch is turned on, human cells will age. When this switch is turned off, human cell aging will slow down, and even reverse cell aging to a certain extent." Liu Lin explained that there are some genes regulating aging in organisms, which has become the consensus of modern medicine. For example, the main function of some genes is to monitor cell status and timely cause cell aging or death, so as to prevent cell carcinogenesis. The dysregulation of the expression of these genes will lead to the acceleration of physical decline. In addition, in the process of aging, some repetitive sequences sealed in our genome and even endogenous viral elements will be activated. They will stimulate the natural immune response of cells, trigger chronic inflammation of tissues and even the body, and lead to aging. The research on DNA damage repair has not stopped. "DNA damage can lead to cell aging. Young cells have a strong DNA repair mechanism. Whether it is base pairs or whole fragments, they can repair themselves well." Liu Lin said that once there are too many injuries, such as chemotherapy drugs and radiation, the cells cannot repair themselves. After DNA damage, some DNA fragments will run from the nucleus to the cytoplasm, causing a series of immune and inflammatory reactions. "Even if we know how to repair DNA base mutations, how to use them to fight cell aging and understand the regulatory mechanism, it is still very difficult." Liu Lin believes that there are some methods for gene repair and gene editing in vitro experiments, but a lot of research is needed to study its safety and effectiveness in vivo cells. In addition, in recent years, epigenetic inhibition of transposon to prevent its activation in the genome is also an important research direction of anti-aging. The human genome contains tens of thousands of transposon sequences, one of the genetic units, which will jump into the genome if the inhibition is released. Transposons, which have long been regarded as a part of junk DNA, have been proved to affect gene expression, including gene expression causing cell aging. At the same time, damaged DNA fragments will also dissociate in the cytoplasm, trigger immune inflammatory reaction and have a great impact on cell aging. The regulation of organelle lysosome is also a new research direction of aging. Liu Lin said that after cell aging, a lot of garbage will be left in the cell. If the cells do not remove these garbage, they will cause cell aging or death. To ensure the youth of cells, we should remove these garbage in time to prevent it from damaging organelles and genome. Lysosomes in cells can wrap garbage through the membrane system through autophagy or mitochondrial autophagy, and then digest, remove or discharge it out of cells. "Applying this principle, some small molecule candidate drugs are in the market development stage. These small molecules can remove the garbage generated by cell aging, which may be helpful for delaying aging and tumor treatment." Liu Lin introduced. New research confirms that inflammation is related to human aging In the study published in science, researchers collected tissue samples from 88 rock fish species and sequenced their genomes using sequencing technology. The team found that longer lived species have more immune regulatory genes, especially a group of genes called lactolipophilins. The researchers also looked for more common DNA variations in long-lived fish to reveal which factors are associated with human aging. Finally, researchers found 137 gene variants related to longevity. After excluding some gene variants that have no direct impact on longevity, they finally determined that other variants related to longevity mainly involve three types of genes: the number of genes that repair DNA increases; Mutations in multiple genes that regulate insulin; Enrichment of genes regulating the immune system. "This study once again confirms that inflammation is the root of everything. The immune system is involved in regulating inflammation, and the increase of inflammation is related to human aging." Liu Lin explained that the tumor also originated from inflammation at the beginning, and aging also originated from inflammation. The main cause of inflammation may be the problem of mitochondrial function, the garbage in organelles may not be cleared, or it is caused by endogenous and exogenous viruses. Telomere shortening and damaged terminal granules will also induce inflammatory response. The results of this study are consistent with the previous research directions of delaying aging, such as DNA repair, regulating immunity and so on. Through this study, some genes can be used as therapeutic targets for age-related injuries. As the researchers of the study said, "we have the opportunity to observe nature, see how natural adaptation affects life expectancy, and then think about how the same genes play a role in our own bodies." (Xinhua News Agency)