Principles of the Molecular and Cellular Mechanisms of Aging.

Aging can be defined as a state of progressive functional decline accompanied by an increase in mortality. Time-dependent accumulation of cellular damage, namely lesions and mutations in the DNA and misfolded proteins, impair organellar and cellular function. Ensuing cell fate alterations lead to the accumulation of dysfunctional cells and hamper homeostatic processes, thus limiting regenerative potential; trigger low-grade inflammation; and alter intercellular and intertissue communication. The accumulation of molecular damage together with modifications in the epigenetic landscape, dysregulation of gene expression, and altered endocrine communication, drive the aging process and establish age as the main risk factor for age-associated diseases and multimorbidity.

Dataset of the properties of polyethylene (PE) blends of different densities mixed with post-consumer recycled polyethylene (PCRPE).

This paper compiles polymer characterization data collected from polyethylene (PE) blends composed of different densities (low-density, LDPE, linear low-density, LLDPE, medium-density, MDPE, and high-density, HDPE) and post-consumer recycled polyethylene (PCRPE), as presented by Cecon et al. (2021). The data were collected from injection molded samples submitted to several physical, thermal, and mechanical characterization techniques, including density, melt flow rate (MFR), thermogravimetric analysis, mechanical testing, and Fourier transform infrared spectroscopy. As there is a significant urgency in recycled polymer utilization in new consumer products from consumers, companies, and governments, the dataset herein presented can be a valuable tool for manufacturers, brand owners, and polymer engineers to model and anticipate different polymer properties associated with the increased use of PCRPE.

DNA damage responses in ageing.

Ageing appears to be a nearly universal feature of life, ranging from unicellular microorganisms to humans. Longevity depends on the maintenance of cellular functionality, and an organism's ability to respond to stress has been linked to functional maintenance and longevity. Stress response pathways might indeed become therapeutic targets of therapies aimed at extending the healthy lifespan. Various progeroid syndromes have been linked to genome instability, indicating an important causal role of DNA damage accumulation in the ageing process and the development of age-related pathologies. Recently, non-cell-autonomous mechanisms including the systemic consequences of cellular senescence have been implicated in regulating organismal ageing. We discuss here the role of cellular and systemic mechanisms of ageing and their role in ageing-associated diseases.

The bystander effect contributes to the accumulation of senescent cells in vivo.

Senescent cells accumulate with age in multiple tissues and may cause age-associated disease and functional decline. In vitro, senescent cells induce senescence in bystander cells. To see how important this bystander effect may be for accumulation of senescent cells in vivo, we xenotransplanted senescent cells into skeletal muscle and skin of immunocompromised NSG mice. 3 weeks after the last transplantation, mouse dermal fibroblasts and myofibres displayed multiple senescence markers in the vicinity of transplanted senescent cells, but not where non-senescent or no cells were injected. Adjacent to injected senescent cells, the magnitude of the bystander effect was similar to the increase in senescence markers in myofibres between 8 and 32 months of age. The age-associated increase of senescence markers in muscle correlated with fibre thinning, a widely used marker of muscle aging and sarcopenia. Senescent cell transplantation resulted in borderline induction of centrally nucleated fibres and no significant thinning, suggesting that myofibre aging might be a delayed consequence of senescence-like signalling. To assess the relative importance of the bystander effect versus cell-autonomous senescence, we compared senescent hepatocyte frequencies in livers of wild-type and NSG mice under ad libitum and dietary restricted feeding. This enabled us to approximate cell-autonomous and bystander-driven senescent cell accumulation as well as the impact of immunosurveillance separately. The results suggest a significant impact of the bystander effect for accumulation of senescent hepatocytes in liver and indicate that senostatic interventions like dietary restriction may act as senolytics in immunocompetent animals.