The Molecular Floodgates of Stress-Induced Senescence Reveal Translation, Signalling and Protein Activity Central to the Post-Mortem Proteome.

The transitioning of cells during the systemic demise of an organism is poorly understood. Here, we present evidence that organismal death is accompanied by a common and sequential molecular flood of stress-induced events that propagate the senescence phenotype, and this phenotype is preserved in the proteome after death. We demonstrate activation of "death" pathways involvement in diseases of ageing, with biochemical mechanisms mapping onto neurological damage, embryonic development, the inflammatory response, cardiac disease and ultimately cancer with increased significance. There is sufficient bioavailability of the building blocks required to support the continued translation, energy, and functional catalytic activity of proteins. Significant abundance changes occur in 1258 proteins across 1 to 720 h post-mortem of the 12-week-old mouse mandible. Protein abundance increases concord with enzyme activity, while mitochondrial dysfunction is evident with metabolic reprogramming. This study reveals differences in protein abundances which are akin to states of stress-induced premature senescence (SIPS). The control of these pathways is significant for a large number of biological scenarios. Understanding how these pathways function during the process of cellular death holds promise in generating novel solutions capable of overcoming disease complications, maintaining organ transplant viability and could influence the findings of proteomics through "deep-time" of individuals with no historically recorded cause of death.

Femur associated with the Deep Skull from the West Mouth of the Niah Caves (Sarawak, Malaysia).

The skeletal remains of Pleistocene anatomically modern humans are rare in island Southeast Asia. Moreover, continuing doubts over the dating of most of these finds has left the arrival time for the region's earliest inhabitants an open question. The unique biogeography of island Southeast Asia also raises questions about the physical and cultural adaptations of early anatomically modern humans, especially within the setting of rainforest inhabitation. Within this context the Deep Skull from the West Mouth of the Niah Caves continues to figure prominently owing to its relative completeness and the greater certainty surrounding its geological age. Recovered along with this partial cranium in 1958 were several postcranial bones including a partial femur which until now has received little attention. Here we provide a description and undertake a comparison of the Deep Skull femur finding it to be very small in all of its cross-sectional dimensions. We note a number of size and shape similarities to the femora of Indigenous Southeast Asians, especially Aeta people from the Philippines. We estimate its stature to have been roughly 145-146 cm and body mass around 35 kg, confirming similarities to Aeta females. Its extreme gracility indicated by low values for a range of biomechanical parameters taken midshaft meets expectations for a very small (female) Paleolithic East Asian. Interestingly, the second moment of area about the mediolateral axis is enlarged relative to the second moment of area about the anteroposterior axis, which could potentially signal a difference in activity levels or lifestyle compared with other Paleolithic femora. However, it might also be the result of sexual dimorphism in these parameters as well as possibly reflecting changes associated with aging.