Proteases are a set of enzymes that have been involved in multiple biological processes throughout evolution. Among them, extracellular matrix (ECM) remodeling has emerged as one of the most relevant functions exerted by these proteins, being essential in the regulation of critical events such as embryonic development or tissue homeostasis. Hence, it is not surprising that dysregulation in any protease function that affects ECM homeostasis may contribute to the aging process. Matrix metalloproteinases (MMPs) are one of the most important families of proteases involved in the tight control of ECM remodeling over time. In this review, we will discuss how MMPs and other proteases alter ECM composition and mechanical properties in aging, thereby affecting stem cell niches and the development of senescent phenotypes. Finally, we will summarize recent findings that associate MMPs with the development of age-related diseases, such as neurodegenerative disorders.
Giant tortoises are amongst the longest-lived vertebrate animals and as
such provide an excellent model to study traits like longevity and age-related
diseases. However, genomic and molecular evolutionary information on giant
tortoises is scarce. Here, we describe a global analysis of the genomes of
Lonesome George, the iconic last member of
Chelonoidis
abingdonii
, and the Aldabra giant tortoise (
Aldabrachelys
gigantea
). The comparison of these genomes to those of related
species, using both unsupervised and supervised analyses, led us to detect
lineage-specific variants affecting DNA repair genes, inflammatory mediators and
genes related to cancer development. Our study also hints at specific
evolutionary strategies linked to increased lifespan and expands our
understanding of the genomic determinants of ageing. These new genome sequences
also provide important resources to help the efforts for restoration of giant
tortoise populations.
Model organisms have provided fundamental evidence that aging can be delayed and longevity extended. These findings gave rise to a new era in aging research aimed at elucidating the pathways and networks controlling this complex biological process. The identification of 9 hallmarks of aging has established a framework to evaluate the relative contribution of each hallmark and the interconnections among them. In this review, we revisit these hallmarks with the information obtained exclusively through the generation of genetically modified mouse models that have a significant impact on the aging process. We discuss within each hallmark those interventions that accelerate aging or that have been successful at increasing lifespan, with the final goal of identifying the most promising antiaging avenues based on the current knowledge provided by in vivo models.
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