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Replicative Cell Senescence02:15

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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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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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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 mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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Induction and Validation of Cellular Senescence in Primary Human Cells
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Cellular senescence: Implications for metabolic disease.

Marissa J Schafer1, Jordan D Miller2, Nathan K LeBrasseur1

  • 1Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, 55905, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, 55905, USA.

Molecular and Cellular Endocrinology
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Cellular senescence, a key aging process, is linked to obesity and metabolic diseases. Further research is needed to understand its complex role in multi-organ diseases.

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AgingDiabetesExerciseInflammationObesitySenolytics

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Area of Science:

  • Cellular and Molecular Biology
  • Aging Research
  • Metabolic Disease

Background:

  • Obesity and aging drive a rise in related diseases, necessitating research into underlying biological processes.
  • Cellular senescence, a stress-induced growth arrest state, is linked to aging and abnormally activated by obesity.
  • Senescent cells exhibit phenotypic markers crucial for understanding their role in tissue pathogenesis.

Purpose of the Study:

  • To investigate the role of cellular senescence in obesity- and aging-related diseases.
  • To explore the potential of targeting senescent cells as a therapeutic strategy for metabolic disorders.

Main Methods:

  • Identification of senescent cell biomarkers in various tissues.
  • Analysis of senescent cell abundance and behavior in metabolic disease contexts.
  • Review of existing literature on the dual role of senescent cells.

Main Results:

  • Biomarkers for senescent cells were found in key metabolic tissues like fat, liver, muscle, pancreas, and cardiovascular tissue.
  • Altering senescent cell abundance or behavior presents a potential therapeutic avenue.
  • The role of senescent cells can be context-dependent, with both protective and detrimental effects observed.

Conclusions:

  • Cellular senescence is implicated in multi-organ diseases associated with obesity and aging.
  • Targeting senescent cells may offer novel therapeutic strategies for metabolic diseases.
  • Additional research is vital to elucidate the complex, context-dependent functions of senescent cells in disease.