There have been enough cell death modes delineated in the biomedical literature to befuddle all cell death researchers. Mulling over cell death from the viewpoints of the host tissue or organ and of the host animal, we construe that there should be only two physiological cell death modes, i.e. apoptosis and senescent death (SD), as well as two pathological modes, i.e. necrosis and stress-induced cell death (SICD). Other death modes described in the literature are ad-hoc variants or coalescences of some of these four basic ones in different physiological or pathological situations. SD, SICD and necrosis kill useful cells and will thus trigger regeneration, wound healing and probably also scar formation. SICD and necrosis will likely instigate inflammation as well. Apoptosis occurs as a mechanism to purge no-longer useful cells from a tissue via phagocytosis by cells with phagocytic ability that are collectively tagged by us as scavengers, including macrophages; therefore apoptosis is not followed by regeneration and inflammation. The answer for the question of “who dies” clearly differentiates apoptosis from SD, SICD and necrosis, despite other similarities and disparities among the four demise modes. Apoptosis cannot occur in cell lines in vitro, because cell lines are immortalized by reprogramming the death program of the parental cells, because in culture there lack scavengers and complex communications among different cell types, and because culture condition is a stress to the cells. Several issues of cell death that remain enigmatic to us are also described for peers to deliberate and debate.

Aims This study was designed to explore the expression and distribution of silent information regulator 1 (SIRT1) and superoxide dismutase 1 (SOD-1) in various regions of the brains of patients with Alzheimer’s disease (AD), as well as to assess potential correlations between the levels of these proteins and also between these proteins and the Braak stage of AD. Methods In the temporal and frontal cortices, hippocampus and cerebellum of 10 patients with AD and 10 age-matched control subjects, expression of SIRT1 and SOD-1, together with histopathology, were assessed by immunohistochemical and immunofluorescent stainings. Relationships between variables were examined with the Pearson correlation test. Results The numbers of both SIRT1-positive and SOD-1-positive neurons and integrated optical density of immunohistochemical staining for these proteins in the temporal and frontal cortices, and hippocampus of patients with AD were significantly decreased than those in corresponding controls. In the case of the cerebellum, very weak expression of SIRT1 and obvious expression of SOD-1 were observed in granule cells, with no significant difference between AD and the control group. Interestingly, the protein levels between SIRT1 and SOD-1, as well as the level of SIRT1 or SOD-1 and Braak stage, were significantly correlated in neurons in all regions of the AD brains investigated except for the cerebellum. Conclusions These findings indicate that the reduced level of SIRT1 in the brains of patients with AD may be related to the decline in SOD-1 and neuropathological changes of this disorder.

In the study, we examined whether the silent information regulator 1 (SIRT1) can attenuate oxidative stress in the brains of mice carrying the APP/PS1 double mutation and/or in primary neonatal rat neurons exposed to oligomers of amyloid-β peptide (A