Reproductive-cell cycle theory

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The reproductive-cell cycle theory posits that the hormones that regulate reproduction act in an antagonistic pleiotrophic manner to control aging via cell cycle signaling; promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence. [1] Rather than seeing aging as a loss of functionality as we get older, this theory defines aging as any change in an organism over time, as evidenced by the fact that if all chemical reactions in the body were stopped, no change, and thus no aging, would occur. Since the most important change in an organism through time is the chemical reactions that result in a single cell developing into a multicellular organism, whatever controls these chemical reactions that regulate cell growth, development, and death, is believed to control aging. The theory argues that these cellular changes are directed by reproductive hormones of the hypothalamic-pituitary-gonadal axis (HPG axis). Receptors for reproductive hormones (such as estrogens, progestogens, androgens and gonadotropins) have been found to be present in all tissues of the body. Thus, HPG axis hormones normally promote growth and development of the organism early in life in order to achieve reproduction. Hormones levels then begin to change in men around age 30 and more abruptly in women when they reach menopause, around age 50. When the HPG axis becomes unbalanced, cellular growth and development is dysregulated, and cell death and dysfunction can occur, both of which can initiate senescence, the accumulated damage to cells, tissues, and organs that occurs with the passage of time and that is associated with functional loss during aging.

Evidence supporting this theory comes from disease studies showing that women who reach menopause later have less heart disease and stroke, less dementia, and less osteoporosis, supporting the theory that the longer the HPG axis is in balance, the less likely one is to develop age-related diseases. Conversely, early surgical menopause has been demonstrated to increase the incidence of these diseases. However, the most compelling supportive evidence is from studies of Hormone Replacement Therapy (HRT). Research with women and men undertaking HRT has shown that taking sex hormones that are biologically identical to human hormones delays the onset, decreases the incidence of, and can reverse the course of age related illnesses such as heart disease, Alzheimer's disease, osteoporosis, and some types of cancer. However, only biological hormones appear to have these effects. The use of non-human or synthetic hormones has been shown to increase the risk of certain of these diseases. Compellingly, 18 studies have demonstrated an increase in longevity for those women taking HRT.

Further studies in support of the theory have shown that suppressing the HPG axis, such as when organisms experience either caloric restriction, cold, or exercise stress, increases lifespan. This is thought to be an evolutionary conserved mechanism that allows organisms to suppress HPG axis signaling and reproduction, thereby conserving reproductive resources (germ cells) for a later time when the environment is better suited to raising offspring. By having the same hormones regulate both reproduction and aging, an animal is able to modulate its fertility and its rate of aging based on environmental conditions. [1]

Recent parabiosis studies prove many of the tenets of the Reproductive Cell-Cycle Theory of Aging. In these experiments, where a young mouse is coupled surgically with an aged mouse, circulating factors from the young mouse rejuvenates the tissues of the old mice. In particular, these studies indicate the importance of circulating factors in regulating the maintenance of neuronal (Villeda et al., 2011), vascular (Katsimpardi et al., 2014), muscular and liver (Conboy et al., 2005; Sinha et al., 2014) structure and function.

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Outline of biology Outline of subdisciplines within biology

Biology – The natural science that studies life. Areas of focus include structure, function, growth, origin, evolution, distribution, and taxonomy.

Endometrium Inner mucous membrane of the mammalian uterus

The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer; the functional layer thickens and then is shed during menstruation in humans and some other mammals, including apes, Old World monkeys, some species of bat, the elephant shrew and the Cairo spiny mouse. In most other mammals, the endometrium is reabsorbed in the estrous cycle. During pregnancy, the glands and blood vessels in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the placenta, which supplies oxygen and nutrition to the embryo and fetus. The speculated presence of an endometrial microbiota has been argued against.

Estrogen Primary female sex hormone

Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy.

Ovary Female reproductive organ that produces egg cells

The ovary is an organ found in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary found on each side of the body. The ovaries also secrete hormones that play a role in the menstrual cycle and fertility. The ovary progresses through many stages beginning in the prenatal period through menopause. It is also an endocrine gland because of the various hormones that it secretes.

Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 48 and 52. Medical professionals often define menopause as having occurred when a woman has not had any menstrual bleeding for a year. It may also be defined by a decrease in hormone production by the ovaries. In those who have had surgery to remove their uterus but still have ovaries, menopause may be considered to have occurred at the time of the surgery or when their hormone levels fell. Following the removal of the uterus, symptoms typically occur earlier, at an average of 45 years of age.

Senescence Deterioration of function with age

Senescence or biologicalaging is the gradual deterioration of functional characteristics in living organisms. The word senescence can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence involves an increase in death rates and/or a decrease in fecundity with increasing age, at least in the latter part of an organism's life cycle.

Estradiol Chemical compound

Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of female secondary sexual characteristics such as the breasts, widening of the hips and a female-associated pattern of fat distribution. It is also important in the development and maintenance of female reproductive tissues such as the mammary glands, uterus and vagina during puberty, adulthood and pregnancy. It also has important effects in many other tissues including bone, fat, skin, liver, and the brain.

Follicle-stimulating hormone Gonadotropin that regulates the development of reproductive processes

Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and luteinizing hormone (LH) work together in the reproductive system.

Anti-Müllerian hormone Mammalian protein found in Homo sapiens

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Hypothalamic–pituitary–gonadal axis

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Ageing Biological process of getting older

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Antagonistic pleiotropy hypothesis Proposed evolutionary explanation for senescence

The antagonistic pleiotropy hypothesis was first proposed by George C. Williams in 1957 as an evolutionary explanation for senescence. Pleiotropy is the phenomenon where one gene controls for more than one phenotypic trait in an organism. Antagonistic pleiotropy is when one gene controls for more than one trait, where at least one of these traits is beneficial to the organism's fitness early on in life and at least one is detrimental to the organism's fitness later on due to a decline in the force of natural selection. The theme of G.C. William's idea about antagonistic pleiotropy was that if a gene caused both increased reproduction in early life and aging in later life, then senescence would be adaptive in evolution. For example, one study suggests that since follicular depletion in human females causes both more regular cycles in early life and loss of fertility later in life through menopause, it can be selected for by having its early benefits outweigh its late costs.

Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal atrophy, accelerated skin aging, vaginal dryness, decreased muscle mass, sexual dysfunction, and bone loss. They are in large part related to the diminished levels of sex hormones that occur during menopause.

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Estrogen and neurodegenerative diseases

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Judith Campisi is an American biochemist and cell biologist. She is a professor of biogerontology at the Buck Institute for Research on Aging. She is also a member of the SENS Research Foundation Advisory Board and an adviser at the Lifeboat Foundation. She is co-editor in chief of the Aging Journal, together with Mikhail Blagosklonny and David Sinclair, and founder of the pharmaceutical company Unity Biotechnology. She is listed in Who's Who in Gerontology. She is widely known for her research on how senescent cells influence aging and cancer — in particular the Senescence Associated Secretory Phenotype (SASP).

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References

  1. 1 2 Bowen RL, Atwood CS (2011). "The reproductive-cell cycle theory of aging: an update". Experimental Gerontology. 46 (2): 100–107. doi:10.1016/j.exger.2010.09.007. PMID   20851172. S2CID   20998909.