Biology subjects

Bascom, C.

Publications and source records attributed to Bascom, C..

3 recordsLinked to original sources

bioRxiv2022

Cell Senescence-Independent Ageing of Human Skin

Skin ageing is defined in part by collagen depletion and fragmentation that leads to a loss of mechanical tension. This is currently believed to reflect, in part, the accumulation of senescent cells. We compared the expression of genes and proteins for components of the extracellular matrix (ECM) as well as their regulators and found that senescent cells produced more matrix metalloproteinases (MMPs) than proliferating cells from adult and neonatal donors. This was consistent with senescent cells contributing to increased matrix degradation with age; however, cells from adult donors proved significantly less capable of producing new collagen than neonatal or senescent cells, and they showed significantly lower myofibroblast activation as determined by the marker -SMA. Functionally, adult cells also showed slower migration than neonatal cells. We concluded that while increased collagen degradation with age might reflect senescent cell accumulation, the reduced collagen production that prevents the skin from maintaining homeostasis must reflect senescence-independent processes.

molecular biology↗

bioRxiv2022

Heterologous expression of a lycophyte protein enhances angiosperm seedling vigor

Seedling vigor is a key agronomic trait that determines juvenile plant performance. Angiosperm seeds develop inside fruits and are connected to the mother plant through vascular tissues. Their formation requires plant-specific genes, such as BREVIS RADIX (BRX) in Arabidopsis thaliana roots. BRX family proteins are found throughout the angiosperms but also occur in non-vascular bryophytes and non-seed lycophytes. They consist of four conserved domains, including the tandem "BRX-domains". We found that bryophyte or lycophyte BRX homologs can only partially substitute for Arabidopsis BRX (AtBRX) because they miss key features in the linker between the BRX-domains. Intriguingly however, expression of a BRX homolog from the lycophyte Selaginella moellendorffii (SmBRX) in A. thaliana wildtype background confers robustly enhanced root growth vigor that persists throughout the life cycle. This effect can be traced back to a substantial increase in seed and embryo size, and can be reproduced with a modified, "SmBRX-like" variant of AtBRX. Our results thus suggest that BRX variants could serve as biotechnological tools to boost seedling vigor and shed light on the activity of ancient, non-angiosperm BRX family proteins.

plant biology↗

bioRxiv2020

Autophagy promotes cell and organismal survival by maintaining NAD(H) pools

Autophagy is an essential catabolic process that promotes clearance of surplus or damaged intracellular components1. As a recycling process, autophagy is also important for the maintenance of cellular metabolites during periods of starvation2. Loss of autophagy is sufficient to cause cell death in animal models and is likely to contribute to tissue degeneration in a number of human diseases including neurodegenerative and lysosomal storage disorders3-7. However, it remains unclear which of the many cellular functions of autophagy primarily underlies its role in cell survival. Here we have identified a critical role of autophagy in the maintenance of nicotinamide adenine dinucleotide (NAD+/NADH) levels. In respiring cells, loss of autophagy caused NAD(H) depletion resulting in mitochondrial membrane depolarisation and cell death. We also found that maintenance of NAD(H) is an evolutionary conserved function of autophagy from yeast to human cells. Importantly, cell death and reduced viability of autophagy-deficient animal models can be partially reversed by supplementation with an NAD(H) precursor. Our study provides a mechanistic link between autophagy and NAD(H) metabolism and suggests that boosting NAD(H) levels may be an effective intervention strategy to prevent cell death and tissue degeneration in human diseases associated with autophagy dysfunction.

cell biology↗