Date Published: May 10, 2018
Publisher: Impact Journals
Author(s): Alexander Klimovich, Arvid Rehm, Jörg Wittlieb, Eva-Maria Herbst, Ricardo Benavente, Thomas C.G. Bosch.
The cnidarian Hydra is known for its unlimited lifespan and non-senescence, due to the indefinite self-renewal capacity of its stem cells. While proteins of the Lamin family are recognized as critical factors affecting senescence and longevity in human and mice, their putative role in the extreme longevity and non-senescence in long-living animals remains unknown. Here we analyze the role of a single lamin protein in non-senescence of Hydra. We demonstrate that proliferation of stem cells in Hydra is robust against the disturbance of Lamin expression and localization. While Lamin is indispensable for Hydra, the stem cells tolerate overexpression, downregulation and mislocalization of Lamin, and disturbances in the nuclear envelope structure. This extraordinary robustness may underlie the indefinite self-renewal capacity of stem cells and the non-senescence of Hydra. A relatively low complexity of the nuclear envelope architecture in basal Metazoa might allow for their extreme lifespans, while an increasing complexity of the nuclear architecture in bilaterians resulted in restricted lifespans.
The freshwater polyp Hydra belongs to the Cnidaria phylum, and represents a rare case of an animal with extreme longevity. It demonstrates unlimited clonal growth with no detectable signs of senescence, such as age-dependent increase in mortality or decrease in fertility, and thus is considered as non-senescent [1–4]. Hydra body is made of cells of three lineages, originating from unipotent ectodermal and endodermal epithelial stem cells, and from multipotent interstitial stem cells (Fig. 1A–C). In contrast to most other animals, stem cells in Hydra indefinitely maintain their self-renewal capacity, thus sustaining non-senescence and everlasting asexual growth [5,6]. While unlimited self-renewal capacity of the stem cells is long recognized fundamental for Hydra’s non-senescence, the underlying molecular mechanisms remain poorly understood. So far, the transcriptional factor FoxO was found as critical regulator of Hydra stem cell homeostasis and longevity, supporting the view that components of the insulin/insulin-like growth factor signaling pathways govern lifespan throughout the animal kingdom [7–10]. Several other transcriptional factors, such as POU domain-containing proteins and Myc family proteins, are supposed to contribute to the non-aging of Hydra and other cnidarians [11,12]. However, the putative effector molecules downstream from these transcriptional factors that might contribute to the sustained stem-cell activity and non-senescence in Hydra remain unclear.
A vast diversity of ageing patterns and lifespans has been reported across the animal kingdom, from fast-ageing short-living species as mayflies and turquoise killifish to species with a remarkable longevity and a negligible senescence – as clams and Hydra [4,41–43]. Studying age-related genes and genetic pathways across distant animal phyla, and especially in the species at the extremes of the lifespan range, may be instrumental in uncovering fundamental principles of the aging and lifespan control. It allows identifying mechanisms shared between the distant phyla (“public”) and those specific to certain evolutionary lineages (“private”) . Extreme longevity of cnidarians makes these animals excellent models for getting insights into the molecular basics of ageing and lifespan control, and to understand the evolution of extended lifespans [45,46]. In the recent decade research on the freshwater polyp Hydra revealed several genes and cellular processes enabling Hydra to decouple the aging process from its life history [9,47]. Here, by gain- and loss-of-function experiments we show that although the single Lamin protein is indispensable for Hydra, similarly to B-type Lamins in other model organisms [27,48–50], Hydra cells appear invulnerable to the changes in Lamin expression level and localization. Since Hydra has only one lamin gene, any compensatory effects from other lamin homologs can be excluded. In bilaterian animals, on the contrary, in spite of the existence of multiple lamin genes (two in Drosophila, three to four in vertebrates [35,37]) and a potential redundancy in their function, the nuclear lamina appears to be extremely vulnerable. Overexpression of Lamin A or B1 [51,52], overexpression of the truncated Lamins lacking CaaX-box , silencing of the lamin A/C or B expression [28,53,54], as well as inactivating mutations in the lamin A gene  impair replicative potential of cells and decrease the animal’s lifespan. Remarkably, all the models used in these studies (fly, flatworm, frog, mice and human) belong to the Bilateria clade and display senescence. Hydra belongs to the sister group of Bilateria – the Cnidaria phylum and demonstrates continuous growth and non-senescence, that are characteristic for other pre-bilaterian animals, such as corals and sponges, as well [45,46]. Our observations suggest that non-senescence of pre-bilaterians requires special nuclear anatomy.