Chromosome ends and the theory of marginotomy: implications for reproduction.

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY
Biogerontology Pub Date : 2024-04-01 Epub Date: 2023-11-09 DOI:10.1007/s10522-023-10071-w
Isabel Córdova-Oriz, Alba M Polonio, Isabel Cuadrado-Torroglosa, Lucía Chico-Sordo, Marta Medrano, Juan A García-Velasco, Elisa Varela
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Abstract

Telomeres are the protective structures located at the ends of linear chromosomes. They were first described in the 1930s, but their biology remained unexplored until the early 70s, when Alexey M. Olovnikov, a theoretical biologist, suggested that telomeres cannot be fully copied during DNA replication. He proposed a theory that linked this phenomenon with the limit of cell proliferation capacity and the "duration of life" (theory of marginotomy), and suggested a potential of telomere lenghthening for the prevention of aging (anti-marginotomy). The impact of proliferative telomere shortening on life expectancy was later confirmed. In humans, telomere shortening is counteracted by telomerase, an enzyme that is undetectable in most adult somatic cells, but present in cancer cells and adult and embryonic stem and germ cells. Although telomere length dynamics are different in male and female gametes during gametogenesis, telomere lengths are reset at the blastocyst stage, setting the initial length of the species. The role of the telomere pathway in reproduction has been explored for years, mainly because of increased infertility resulting from delayed childbearing. Short telomere length in ovarian somatic cells is associated to decreased fertility and higher aneuploidy rates in embryos. Consequently, there is a growing interest in telomere lengthening strategies, aimed at improving fertility. It has also been observed that lifestyle factors can affect telomere length and improve fertility outcomes. In this review, we discuss the implications of telomere theory in fertility, especially in oocytes, spermatozoa, and embryos, as well as therapies to enhance reproductive success.

Abstract Image

染色体末端与边缘切除理论:对生殖的启示。
端粒是位于线性染色体末端的保护性结构。它们在20世纪30年代首次被描述,但直到70年代初,理论生物学家阿列克谢·M·奥洛夫尼科夫(Alexey M.Olovnikov)才发现端粒的生物学特性。他提出了一种理论,将这种现象与细胞增殖能力的极限和“寿命”联系起来(边缘切除术理论),并提出了端粒延长预防衰老的潜力(抗边缘切除术)。增殖性端粒缩短对预期寿命的影响后来得到证实。在人类中,端粒缩短被端粒酶抵消,端粒酶是一种在大多数成年体细胞中检测不到的酶,但存在于癌症细胞、成年和胚胎干细胞和生殖细胞中。尽管在配子发生过程中,雄性和雌性配子的端粒长度动态不同,但端粒长度在胚泡阶段会重置,从而设定物种的初始长度。端粒途径在生殖中的作用已经被探索了多年,主要是因为延迟生育导致不孕不育增加。卵巢体细胞端粒长度短与胚胎的生育能力下降和非整倍体率升高有关。因此,人们对旨在提高生育能力的端粒延长策略越来越感兴趣。还观察到,生活方式因素可以影响端粒长度并改善生育结果。在这篇综述中,我们讨论了端粒理论在生育能力中的意义,特别是在卵母细胞、精子和胚胎中,以及提高生育成功率的疗法。
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来源期刊
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
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