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Salamander Insights Into Ageing and Rejuvenation

Maximina H. Yun

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- The axolotl— Ambystoma mexicanum—and the Iberian ribbed newt—Pleurodeles waltl—are two laboratorytractable systems whose adoption has exponentially grown in recent years due to the ease of captive breeding and rearing, efficient transgenesis and genome editing methods, availability of genomic and transcriptomic information, and advanced imaging techniquesBox 1).
- Muscle regeneration relies on progenitors derived from dedifferentiation of mature muscle fibresTanaka et al, 2016), while the lens of the eye is regenerated de novo.
- Still a poorly developed area, recent studies suggest that axolotls employ robust DNA damage response mechanisms to promote proper cell cycle progression upon injury, which may restrict excessive generation of senescent cells in regenerative contexts.
- It is possible that their large genomes provide an additional level of protection against mutagenic challenges, as the presence of extensive noncoding, non-regulatory areas would help ease the mutagenic burden. It is yet unclear if the mechanisms of genome maintenance in salamander cells are more efficient than those found in their mammalian counterparts both in regenerative and homeostatic contexts, whether salamander cells are more resistant to certain types of genome challenges, and how well does this explain their limited senescent cell accumulation and resistance to age-related decay.
- Challenging the link between regeneration and rejuvenation further will require establishing reliable aging biomarkers in salamanders, capable of accurate determinations of tissue age, and leveraging systems approaches to determine the molecular changes that occur with time from individual cells to entire structures and how these are affected by regenerative processes.
- Salamanders offer a wealth of interesting biology, from their seemingly endless regenerative abilities to their extreme lifespans and resistance to cancer and age-related decay.
- The resulting insights will help us further understand the nature of regeneration, ageing and their interconnection, central to the development of rejuvenation strategies of clinical relevance.

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