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Related Concept Videos

Aging01:26

Aging

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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.
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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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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The upper and lower limb initially develops as a small bulge called a limb bud, which appears on the lateral side of the early embryo. The upper limb bud appears near the end of the fourth week of development, with the lower limb bud appearing shortly after.
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Age-related pharmacokinetic changes are extensively documented, but understanding age-related pharmacodynamic alterations is relatively limited. This knowledge gap can be partly attributed to the complexity of developing appropriate measures of drug responses compared to bioanalytical methods for determining drug concentrations.Most information regarding age-related differences in human pharmacodynamics originates from cross-sectional studies. However, these studies assume that observed mean...
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Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Absorption01:22

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As individuals age, their body's physiology evolves, affecting drug pharmacokinetics. The most apparent changes occur in the gastrointestinal tract, where an increase in gastric pH, a delay in gastric emptying, and a reduction in gastrointestinal motility are observed. Remarkably, these changes do not substantially modify the absorption of orally administered drugs, particularly those absorbed via passive diffusion.Transdermal drug delivery emerges as a highly viable method for older adults due...
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Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Distribution01:00

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Drug distribution in the human body is influenced by several factors, including plasma protein concentration, body composition, blood flow, tissue-protein concentration, and tissue fluid pH. Among these, changes in plasma protein concentration and body composition due to aging significantly affect how drugs are distributed within the body. Specifically, aging is associated with a decrease in albumin levels by about 10% and an increase in α1-acid glycoprotein levels. These alterations are...
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Derivation of a Human Brain Organoid with Microglia Development
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A transcriptomic atlas of aged human microglia.

Marta Olah1,2, Ellis Patrick3, Alexandra-Chloe Villani2,4

  • 1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York City, NY, 10032, USA.

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|February 9, 2018
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Researchers identified a unique gene set in aged human microglia, revealing a distinct aging-related microglial phenotype. This finding is crucial for understanding neurodegenerative diseases like Alzheimer's and multiple sclerosis.

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Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • The global population is aging, increasing the urgency to find cures for age-related neurodegenerative diseases.
  • Microglia, immune cells in the brain, are implicated in neurodegeneration, but their aged phenotype is poorly understood.
  • Understanding aged microglia is critical for developing effective treatments for age-related brain diseases.

Purpose of the Study:

  • To identify and characterize the specific gene expression profile of microglia in the aged human brain.
  • To determine if this aged microglial phenotype is associated with known neurodegenerative disease risk genes.
  • To investigate the influence of aging and specific genetic factors (APOE haplotypes) on this microglial phenotype.

Main Methods:

  • Gene expression analysis to identify genes preferentially expressed in aged human microglia.
  • Proteomic validation to confirm the identified gene expression changes at the protein level.
  • Bioinformatic enrichment analysis to assess the association of the identified gene set with neurodegenerative disease susceptibility genes and APOE haplotypes.

Main Results:

  • A distinct gene set, termed HuMi_Aged, was identified, representing a unique aged human microglial phenotype.
  • This HuMi_Aged gene set was confirmed at the protein level.
  • The HuMi_Aged set is enriched in genes associated with Alzheimer's disease and multiple sclerosis susceptibility.
  • Gene expression in this set increases with age and is reduced by the protective APOEε2 haplotype, while APOEε4 shows no effect.

Conclusions:

  • An aging-related microglial phenotype exists in the aged human brain.
  • This phenotype is linked to the genetic underpinnings of major neurodegenerative diseases.
  • The findings provide a foundation for understanding microglial roles in brain aging and disease pathogenesis.