Is the Architecture of the Nuclear Envelope Fundamental to the Evolution of Aging?

Hydra are functionally immortal, given a suitably static environment. They exhibit continual proficient regeneration, and their mortality risk is low and constant over time. As a species they appear near unique in this. Why is aging and imperfect regeneration almost universal among species? One explanation is that environmental change gives aging species an advantage: non-aging species can certain emerge in eras of comparative environmental stability, but will be out-competed when the environment shifts. Other explanations involve the more complex structure in higher species, particularly in the central nervous system, where data must be stored as lasting molecular and cellular structures. Long-term persistence of fine cellular structure and proficient, continual regeneration don’t go well together.

This study looks at the complexity and structure of the nuclear envelope inside cells as a possible dividing line between the few immortal species such as hydra and all of the others. The authors propose that increased complexity of the nuclear structure, and thus its greater vulnerability to certain kinds of molecular damage known to be associated with aging, limits the degree to which longevity and highly proficient regeneration can evolve – though I think that this is certainly something that could be argued either way, and at length.

The freshwater polyp Hydra 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. Hydra body is made of cells of three lineages, originating from unipotent ectodermal and endodermal epithelial stem cells, and from multipotent interstitial stem cells. In contrast to most other animals, stem cells in Hydra indefinitely maintain their self-renewal capacity, thus sustaining non-senescence and everlasting asexual growth.

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. Several other transcriptional factors are supposed to contribute to the non-aging of Hydra. 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.

Studies in bilaterian animals propose proteins of the Lamin family to be the major effector molecules involved in the age-related cellular senescence and, hence, in the genetic control of ageing and lifespan. These highly conserved intermediate filament proteins form a complex network at the inner nuclear membrane, arrange the nuclear architecture and orchestrate multiple nuclear processes, such as DNA replication and repair, chromatin condensation, and transcription. Importantly, bilaterian cells are highly sensitive to the nuclear lamina disturbances. Decline in the expression level of Lamin B1 and increase of an aberrant Prelamin A isoform are associated with the age-dependent alterations in the nuclear lamina morphology and chromatin organization observed upon physiological ageing in mammals and invertebrates.

A homologue of vertebrate lamin B genes has been identified in Hydra, yet no efforts have been reported addressing the role of Lamin in cnidarian longevity. Here we present detailed analysis of the single Hydra lamin gene (hyLMN), its expression pattern, and distribution and function of its protein product (HyLMN). 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 might allow for the observed extreme lifespans of Hydra, while an increasing complexity of the nuclear architecture in bilaterians resulted in restricted lifespans.

Link: https://doi.org/10.18632/aging.101440

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