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UPS impairment has been reported in aging [13], brain ischemia [14], [15], Huntington's disease (HD) [16] [19], Cruetzfeldt-Jakob disease (CJD), Alzheimer's disease (AD) [20] [23], Amyotrophic Lateral Sclerosis (ALS) [24], and Parkinson's disease (PD) [25] [30].
In support of the hypotheses, increased levels of ROS have been reported in aging BMSC [ 14].
However, this effect has not been reported in aging models of Leydig cells.
An overall decrease in chaperone-mediated autophagy has also been reported in aging rat liver cells.
Elevated levels of DNA damage have been reported in aging epidermal stem cells and hematopoietic stem cells.
These alterations likely reflect increased metabolite production, together with decreased metabolite clearance and reduced CSF turnover, which has been reported in aging populations and Alzheimer's disease [ 87, 88].
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An increased incidence of apoptosis, as well as the expression of pro-apoptotic proteins and mitochondrially-mediated cell death signaling, have been reported in aged skeletal muscle [ 18- 20].
For example changes in brain glycoprotein composition were reported in aging brain [ 4].
Further, a lesser memory impairment in LLS compared to AD has also been reported in age-matched patients [5], [7].
As far as age is concerned, the highest prevalence of deformity has been reported in age group of more than 60 years [ 24].
Although apoptosis has been reported in age-related IVD degeneration, with higher rates of apoptosis present in older individuals [ 10], no studies, to date, have comprehensively investigated cellular senescence in ageing or degenerate IVDs.
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