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Related Concept Videos

Aging01:26

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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.
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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
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Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
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High-dimensional Ageome Representations of Biological Aging across Functional Modules.

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Aging involves complex molecular changes. A new framework, Ageome, measures epigenetic aging across many pathways, offering a detailed view beyond single biological age estimates for better insights into aging and disease.

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Area of Science:

  • Gerontology
  • Computational Biology
  • Epigenetics

Background:

  • Aging is characterized by molecular changes leading to functional decline and increased disease risk.
  • Current epigenetic aging clocks provide single age estimates but lack mechanistic detail.
  • Biological aging may be better represented by the collective aging of multiple functional modules.

Purpose of the Study:

  • To challenge the paradigm of single biological age estimates.
  • To introduce Ageome, a computational framework for multi-pathway epigenetic age measurement.
  • To provide a high-dimensional representation of aging dynamics.

Main Methods:

  • Developed the Ageome computational framework.
  • Applied Ageome to measure epigenetic ages of thousands of molecular pathways in mice and humans.
  • Analyzed longevity intervention models and human cohorts.

Main Results:

  • Ageome provides a high-dimensional view of biological aging across cellular functions.
  • Distinct patterns of pathway-specific age deceleration were observed in longevity interventions.
  • Cell reprogramming showed mixed effects, rejuvenating some modules while accelerating others.
  • Ageome revealed heterogeneity in mortality prediction and improved prediction for age-related diseases like cancer in human cohorts.

Conclusions:

  • The Ageome framework offers a comprehensive and interpretable approach to aging assessment.
  • It provides insights into aging mechanisms and potential intervention targets.
  • Ageome moves beyond single-point biological age estimates for a more nuanced understanding of aging.