Accumulation of damage is generally considered the cause of aging. Interventions that delay aging mobilize mechanisms that protect and repair cellular components. Consequently, research has been focused on studying the protective and homeostatic mechanisms within cells. However, in humans and other multicellular organisms, cells are surrounded by extracellular matrices (ECMs), which are important for tissue structure, function, and intercellular communication. During aging, components of the ECM become damaged through fragmentation, glycation, crosslinking, and accumulation of protein aggregation, all of which contribute to age-related pathologies. Interestingly, placing senescent cells into a young ECM rejuvenates them. Furthermore, we found that many longevity-assurances pathways reactivate de novo synthesis of ECM proteins during aging. This raises the question of what constitutes a young ECM to reverse aging or maintain health? In order to make inroads to answering this question, I suggest a systems-level approach of quantifying the matrisome or ECM compositions reflecting health, pathology, or phenotype and propose a novel term, the "matreotype," to describe this. The matreotype is defined as the composition and modification of ECM or matrisome proteins associated with or caused by a phenotype, such as longevity, or a distinct and acute physiological state, as observed during aging or disease. Every cell type produces its unique ECM. Intriguingly, cancer-cell types can even be identified based on their unique ECM composition. Thus, the matreotype reflects cellular identity and physiological status. Defined matreotypes could be used as biomarkers or prognostic factors for disease or health status during aging with potential relevance for personalized medicine. Treatment with biologics that alter ECM-to-cell mechanotransduction might be a strategy to reverse age-associated pathologies. An understanding of how to reverse from an old to a young matreotype might point toward novel strategies to rejuvenate cells and help maintain tissue homeostasis to promote health during aging.
Green fluorescent protein (GFP) is widely used as a molecular tool to
assess protein expression and localization. In C. elegans, the
signal from weakly expressed GFP fusion proteins is masked by autofluorescence
emitted from the intestinal lysosome-related gut granules. For instance, the GFP
fluorescence from SKN-1 transcription factor fused to GFP is barely visible with
common GFP (FITC) filter setups. Furthermore, this intestinal autofluorescence
increases upon heat stress, oxidative stress (sodium azide), and during aging,
thereby masking GFP expression even from proximal tissues. Here, we describe a
triple band GFP filter setup that separates the GFP signal from
autofluorescence, displaying GFP in green and autofluorescence in yellow. In
addition, yellow fluorescent protein (YFP) remains distinguishable from both the
yellowish autofluorescence and GFP with this triple band filter setup. Although
some GFP intensity might be lost with the triple band GFP filter setup, the
advantage is that no modification of currently used transgenic GFP lines is
needed and these GFP filters are easy to install. Hence, by using this triple
band GFP filter setup, the investigators can easily distinguish autofluorescence
from GFP and YFP in their favorite transgenic C. elegans
lines.
Proper collagen homeostasis is essential for development and aging of any multicellular organism. During aging, two extreme scenarios are commonly occurring: a local excess in collagen deposition, for instance during fibrosis, or a gradual overall reduction of collagen mass. Here, we describe a histological and a colorimetric method to assess collagen levels in mammalian tissues and in the nematode Caenorhabditis elegans. The first method is the polychrome Herovici staining to distinguish between young and mature collagen ratios. The second method is based on hydroxyproline measurements to estimate collagen protein levels. In addition, we show how to decellularize the multicellular organism C. elegans in order to harvest its cuticle, one of two major extracellular matrices, mainly composed of collagen. These methods allow assessing collagen deposition during aging either in tissues or in whole organisms.
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