Defining cognitive superaging in centenarians via an iPSC-based platform
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Citation
Abstract
Centenarians, or individuals that live in excess of 100 years, display remarkable resistance to aging-related diseases such as cardiovascular disease, cancer, and Alzheimer’s disease and related dementias (ADRD). Here, we identify a specialized group of centenarians who have remarkably evaded the consequences of age-related cognitive decline, even at the extremes of longevity. We evaluated clinical history, cognitive benchmark testing, assessments of independence such as activities of daily living and finance management, and molecular assays including biological aging clocks in our determination of this group. These cognitive SuperAgers score at least two decades below their biological age on a variety of tests that involve episodic memory, verbal recall, and cognitive impairment. Here, we created induced pluripotent stem cells (iPSCs) from these subjects and used this platform to create large numbers of neurons from these specialized individuals. We then used these cells, which capture the genetic background of the individual from whom they are created, to investigate and model neurocognitive aging-related diseases in vitro. We performed transcriptomic and functional assays to identify a universal signature of cognitive resilience with the aim to further understand the molecular basis of resistance to disease. An improved understanding of the mechanisms that underlie cognitive SuperAging will allow for the development of novel therapeutics that may improve cognition across a lifetime and provide protection against neurocognitive decline.
Description
2025