In biology and physiology, senescence is a series of dysfunctional processes that follow a period of growth in an organism. The science of geriatrics is particularly concerned with this process of senescence and includes what is called life extension. Cellular senescence is a phenomenon in which cells lose their ability to divide and thus regenerate. As a result of DNA damage in cells, either senescence occurs or self-destructs if the error cannot be corrected. The term aging or longevity is frequently used here as a companion term and similar to senescence. The terms senescence and senescence are now used interchangeably in most articles. Aging is characterized by a diminished ability to cope with stress, an increase in homeostasis, and an increased risk of diseases of old age, including cancer and heart disease. Aging has been defined as "a progressive weakening of bodily functions and an intrinsic age-related process involving loss of vitality and increased susceptibility to illness." As a result, death is the inevitable consequence of aging. Senescence, or biological aging, is the gradual deterioration of the functional properties of an organism. The word senescence may refer to cellular senescence, or to the senescence of the organism as a whole. Organic senescence involves an increase in mortality rates and/or a decrease in fertility rates with age, at least during the latter part of an organism's life cycle. Senescence is the inevitable fate of all multicellular organisms in which both sex and somatic cells divide, but it can be delayed. In 1934, it was discovered that caloric restriction could extend the lifespan of mice by 50%. There are species in which senescence is almost nonexistent, such as Hydra, and the possibility of their immortality has inspired researchers to investigate the field of delaying senescence, and thus delaying age-related diseases. We know that some mutations in humans can cause accelerated diseases of senescence. Environmental factors can also affect aging. For example, excessive exposure to ultraviolet radiation accelerates skin aging. Different parts of the body may age at different rates, and two organisms of the same species may age at different rates, making biological aging and chronological aging two different concepts. There are a number of hypotheses about how aging occurs. Organic aging is the aging of all organisms. Actuarial aging can be defined as the increase in mortality and/or decline in fertility with age. According to the Gompertz-Mackeham Mortality Law, the effect of the age-dependent factor increases steadily with age. In 2013, a group of scientists identified nine common aging markers in organisms, focusing primarily on mammals: Aging is characterized by a decreased ability to respond to stress, increased homeostatic imbalance, and increased risk of age-related diseases including cancer and heart disease. Aging is defined as a gradual decline in physiological function, an intrinsic age-related process in which there is a loss of viability and an increase in vulnerability. Environmental damage occurs at several levels, such as damage to DNA or damage to tissues and cells caused by exposure to oxygen radicals, some of which is irreversible and accumulates over time. Cloning from somatic cells rather than sex cells makes an individual’s life more vulnerable to damage; Dolly the sheep died young from a lung disease, but more data on cloned organisms is needed to measure mortality rates. George Williams writes: “It is remarkable that after this miracle seemed possible, the cyclic complex could not perform the simpler task of preserving what had already been formed.” The rate of aging varies among species; mice, for example, live on average three years, whereas humans currently live 80 years. Almost all organisms age, including bacteria, which have no particular symmetry that allows us to know the resulting bacteria and the bacteria that divide after division. There is a slight aging in some groups, such as the genus Hydra. The flatworm Planaria has the ability to renew its telomeres indefinitely, because it contains a population of highly reproductive stem cells. These planaria are not biologically immortal, but their death rate increases slowly with age. Some species show negative aging, in which the ability to reproduce increases or remains stable, and their death rate decreases with age. Natural selection may favor lethal or deleterious alleles if their effects appear after reproduction. The geneticist J. B. S. Haldane wondered why the dominant mutation that causes Huntington's disease in humans persists and why natural selection has not eliminated it. Huntington's disease onset is on average around age 45, and always ends in death within 10 to 20 years. Haldane hypothesized that in prehistoric times few people survived to age 45, and since only a few of them were found alive, their impact on their cohorts was minimal. Peter Medrow formalized this observation in his mutational accumulation theory of aging. Another theory of aging proposed by George C. Williams is the pleiotropy of opposite phenotypes. A single gene may affect several traits, some of which are important for health early in life but may have negative effects later on. However, since many individuals survive early and fewer later, the identification of these negative effects is poor. Williams suggests the following example: "A gene that encodes proteins that promote bone calcium deposition, which promotes survival in adolescence, may be favored by natural selection, but the same gene promotes calcium deposition in arteries, causing atherosclerosis in the elderly and thus increasing mortality. Thus, the deleterious biological changes of aging result from the selection of pleiotropic genes that are beneficial early in life but become harmful later on in life." The reproductive cell cycle theory proposes that aging is regulated by changes in hormonal signals during an individual's lifetime. Cell damage accumulates over time, but this is balanced by natural selection that removes damaged cells, primarily their DNA. Somatic cells in most multicellular species will eventually encounter what is known as senescence, and will not be able to divide, which may prevent the cell from becoming cancerous. For example, a fibroblast cell can give rise to a maximum of 50 dividing cells, and this limit is known as the Heilich limit. Replication senescence occurs as a result of short telomeres that will eventually lead to a response to DNA damage. Cell senescence may be triggered by elevated reactive oxygen species and activation of oncogenes regardless of telomere length. Many organisms have asymmetric cell division, for example, a stem cell divides to give rise to a stem cell and a non-stem cell, so that cellular debris is not divided equally among the new cells. Cancer cells avoid replication senescence and become immortal. In 85% of tumors, the reason for the absence of senescence is the activation of telomere genes. Senescent cells in multicellular organisms can be eliminated through cell competition, but this increases the risk of cancer, leading to an inevitable dilemma, which presents us with two possibilities: the first is the accumulation of senescent cells that are of no physiological use, and the second is the development of cancer, both of which will lead to increased mortality rates with age. One of the first theories to attempt to explain aging was the heartbeat hypothesis described by Raymond Pearl in 1928, which states that a fast basal metabolic rate corresponds to a small upper age limit.