Abstract
Aging is a cause of cognitive decline in the elderly and the major risk factor for Alzheimer's disease, however, aging people are not all destined to develop into cognitive deficits, the molecular mechanisms underlying this difference in cognition of aging people are obscure. Epigenetic modifications, particularly histone acetylation in the nervous system, play a critical role in regulation of gene expression for learning and memory. An inhibitor of acetyltransferases (INHAT) is reported to suppress histone acetylation via a histone-masking mechanism, and pp32 is a key component of INHAT complex. In the present study, we divided ~18 m-old aged mice into the cognitive-normal and the cognitive-impaired group by Morris water maze, and found that pp32 level was significantly increased in the hippocampus of cognitive-impaired aged mice. The mRNA and protein levels of synaptic-associated proteins decreased with reduced dendrite complexity and histone acetylation. Knockdown of pp32 rescued cognitive decline in cognitive-impaired aged mice with restoration of synaptic-associated proteins, the increase of spine density and elevation of histone acetylation. Our study reveals a novel mechanism underlying the aging-associated cognitive disturbance, indicating that suppression of pp32 might represent a promising therapeutic approach for learning and memory impairments.
Highlights
In the twenty-first century, aging population has emerged as a major demographic trend worldwide
Since aging is associated with cognitive decline, we utilized a mouse model of aging to explore the role of pp32 in learning and memory
By using 12 month-old mice as the control, we performed Morris water maze (MWM)-tests to screen out the cognitive-impaired group (Aged-cognitive impaired (CI)) and cognitive-normal group (Aged-cognitive normal (CN)) from 18-month old aging mice as shown in the methods
Summary
In the twenty-first century, aging population has emerged as a major demographic trend worldwide. Declining fertility, improved health, and longevity, have swelled the older populations dramatically. The global population of people aged 60 and over representing 11 percent of the world’s population, were 680 million people in 2009. They have increased by 10.4 million just since 2007—an average increase of 30,000 each day. By 2050, the 60 and older population will increase from 11 to 22 percent of the world’s population-increasing from 680 million to 2 billion. Aging is the major risk factor for major neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Most people over the age of 70 exhibit some degree of cognitive
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