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Related Concept Videos

Aging01:26

Aging

89
Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
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The Effect of Aging on Tissues01:19

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Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
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Techniques to Induce and Quantify Cellular Senescence
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Identifying novel age-modulating compounds and quantifying cellular aging using novel computational framework for

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    Researchers developed RNAge, a transcriptional score to measure cellular age. This tool helps identify compounds that can modify aging in human pluripotent stem cell (hPSC)-derived cells, advancing research into health span extension.

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    Area of Science:

    • Stem Cell Biology
    • Aging Research
    • Transcriptomics

    Background:

    • Human pluripotent stem cells (hPSCs) offer access to diverse cell types but typically yield fetal-stage identities.
    • Accelerating aging in hPSC-derived lineages and understanding age-related factors are crucial for extending human health span.
    • Developing reliable methods to score cellular age is essential for evaluating age-modifying strategies.

    Purpose of the Study:

    • To establish a transcriptional score (RNAge) for quantifying cellular age in various human tissues and cell types.
    • To validate RNAge's accuracy and specificity across independent datasets and cell lineages.
    • To utilize RNAge to identify novel compounds that modulate cellular aging, including age-inducing and rejuvenating agents.

    Main Methods:

    • Development and validation of the RNAge transcriptional score using RNA-seq data from young versus old primary fibroblasts and human brain tissues.
    • Assessment of RNAge in hPSC-derived cells, including induced neurons (iN), under various reprogramming and age-inducing conditions.
    • In-silico screening of the LINCS L1000 dataset using RNAge as a probe to identify potential age-modifying compounds.

    Main Results:

    • RNAge demonstrated cell and tissue specificity and accurately reflected age-related transcriptional changes.
    • Reprogramming aged fibroblasts to iPSCs reset RNAge, while direct reprogramming to iNs maintained aging signatures.
    • Several novel age-inducing and rejuvenating compounds were identified, and RNAge correlated with distinct cellular hallmarks of aging.

    Conclusions:

    • RNAge provides a simple and effective tool for scoring cellular age and evaluating age-modifying strategies in hPSC-derived lineages.
    • The identified compounds expand the available toolkit for manipulating cellular age, with implications for regenerative medicine and longevity research.
    • This study advances the understanding of cellular aging mechanisms and offers new avenues for therapeutic interventions targeting age-related diseases.