Abstract
Aging is a natural human process. It is uniquely individual, taking into account experiences, lifestyle habits and environmental factors. However, many disorders and syndromes, such as osteoporosis, neurodegenerative disorders, cognitive decline etc., often come with aging. The present study was designed to investigate the possible anti-aging effect of N6-(4-hydroxybenzyl)adenine riboside (T1-11), an adenosine analog isolated from Gastrodia elata, in a mouse model of aging created by D-galactose (D-gal) and the underlying mechanism, as well as explore the role of adenosine signaling in aging. T1-11 activated A2AR and suppressed D-gal- and BeSO4-induced cellular senescence in vitro. In vivo results in mice revealed that T1-11 abated D-gal-induced reactive oxygen species generation and ameliorated cognitive decline by inducing neurogenesis and lowering D-gal-caused neuron death. T1-11 could be a potent agent for postponing senility and preventing aging-related neuroinflammation and neurodegeneration.
Highlights
Aging is a progressive, accumulative and natural phenomenon, associated with multiple and irreversible physiological and pathological changes, including the formation of advanced glycation end-products (AGEs) and free radical damage in cells, tissues and organs of an organism [1]
Previous study indicated that the level of A2AR was lower in the senescence-accelerated prone mouse model (SAMP8) as compared with the senescence-accelerated resistant mouse model (SAMR1) [16]
The present study showed that (1) A2AR inhibition could induce premature senescence and the expression of cellular senescence markers in SH-SY5Y; (2) T1-11 suppressed the cellular senescence of SHSY5Y; (3) T1-11 ameliorated D-gal-induced cognitive decline in mice; and (4) T1-11 treatment elicited neurogenesis as well as reduced neuroinflammation and the expression of cellular senescence markers in the hippocampus of D-gal-induced aging mice
Summary
Accumulative and natural phenomenon, associated with multiple and irreversible physiological and pathological changes, including the formation of advanced glycation end-products (AGEs) and free radical damage in cells, tissues and organs of an organism [1]. Aging is associated with cognitive deterioration, including memory loss and impaired induction of long-term potentiation [3] Several chemical agents, such as beryllium salts and Dgalactose (D-gal), have been reported to cause cellular senescence [4, 5] and syndromes similar to aging [6, 7]. A high dosage of D-gal inhibits the expression of nerve growth factors and their associated proteins, which results in the degeneration of neurons and further impairment of long-term potentiation and neurogenesis in the hippocampus, thereby causing memory dysfunction [5]
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