5.8Senescence and Lifespan

Animals that have passed their breeding period generally undergo senescence; therefore, changes due to senescence are distinguished from disease. Senescence is caused by various factors, including genetic ones. Senescence causes animals to expend their lifespan and eventually die. Different animal species have different lifespans, but all these lifespans are limited, and animals cannot continue to live indefinitely once their lifespans are spent.
Studies of senescence and longevity in various animals have revealed that these phenomena are affected by several genetic factors. One of these factors now attracting attention is a special kind of DNA called "telomeres," which are distributed on the two ends of every chromosome (see Column at the bottom). Telomeres are important structures that protect chromosomes, but the length of telomeres decreases by a constant amount each time the cell divides. Consequently, once a certain limited number of cell divisions have occurred, the telomeres become so short that they can no longer protect the chromosomes. Once that point is reached, further cell division is disabled in order to prevent abnormalities in the chromosomes. Consequently, the lifespan of an animal is completed after a certain number of cell divisions have occurred.
Animal cells originally have mechanisms that repair abnormalities in the molecules from which they are formed. However, these mechanisms deteriorate with age. Consequently, as an animal gets older after its breeding period, dysfunctions of these mechanisms occur and genetic mutations accumulate, leading to diseases. In addition, immune and endocrine functions also deteriorate. Our lifespans are also shortened by various factors such as stress from the environment and excessive calorie intake by overeating.


Telomeres Determine the Limit of the Human Lifespan

The cells that constitute our bodies have a definite lifespan. These lifespans are determined by chromosomal structures called "telomeres" in the chromosomes of cells. Since the lifespans (the limit of the number of times cells can divide) of cells are determined by these structures, our lifespans are unavoidably limited.
Telomeres are a special kind of DNA that is present on both ends of all chromosomes. They act to preserve the structures of the chromosomes and to stabilize their functions. However, part of the telomere is lost each time DNA replicates (Column Fig. 5-2A). Consequently, once a cell divides 60–100 times, the lengths of the telomeres become so short that they can no longer perform these functions. Once this condition has been reached, the possibility of chromosomal abnormalities arises. Therefore, to avoid this problem, further cell division is disabled. Cells that can no longer divide eventually exceed their lifespan, and this causes the limit on our life spans.
It is very rare for normal humans to live until the limit of the lifespan determined by telomeres (about 110 years old, Column Fig. 5-2B). This is because the lifespan of animals is affected by various factors other than telomeres. For example, highly reactive molecules such as reactive oxygen are always being produced in animal bodies. Such molecules oxidize DNA, proteins, fats, etc., and cause gene mutations, cell dysfunction, and mitochondrial abnormalities, thus shortening our lifespan.
However, there are also special cells that can continue to divide indefinitely. Germ cells and cancer cells are typical examples. These cells can continue to divide indefinitely because of the activity of a special enzyme called "telomerase" that exists only in these cells. During DNA replication, this enzyme replicates the lost portion of the telomeres and returns them to their original state (Column Fig. 5-2A).

Column Fig. 5-2. Telomere Reduction and Cell Lifespan

(A) When DNA is replicated during division of normal somatic cells, the telomeres gradually become shorter. Once they diminish to a certain length, cell division ceases. In germ cells and cancer cells, however, DNA replication is not accompanied by telomere reduction because there is an enzyme called "telomerase," which replicates the reduced portions of the telomeres and restores them to their original state. Telomerase has telomere template RNA. Based on this template, the telomerase replicates and replaces the lost portion of the telomere. Consequently, germ cells and cancer cells can continue unlimited cell division.
(B) A graph of the relationship (red solid line) between telomere length and the age of humans based on actual measured values. The red broken line is extrapolated based on the results shown by the solid line.

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