Related Experiment Video

Updated: Mar 20, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
08:15

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model

Published on: June 6, 2025

691

Perspective: Targeting the JAK/STAT pathway to fight age-related dysfunction

Ming Xu1, Tamar Tchkonia1, James L Kirkland1

  • 1Robert and Arlene Kogod Center on Aging, Mayo Clinic, United States.

Pharmacological Research
|June 1, 2016
PubMed

Insights

Cellular senescence, marked by a senescence-associated secretory phenotype (SASP), drives aging dysfunction. Inhibiting the JAK pathway reduces SASP and alleviates age-related tissue problems, improving healthspan.

Area of Science:

  • Cellular and Molecular Biology
  • Gerontology
  • Immunology

Background:

  • Cellular senescence is a state of irreversible growth arrest that accumulates in tissues with age.
  • Senescent cells exhibit a senescence-associated secretory phenotype (SASP), releasing inflammatory factors that disrupt tissue homeostasis.
  • The SASP contributes to age-related local and systemic dysfunction.

Purpose of the Study:

  • To investigate the role of the JAK pathway in regulating the SASP.
  • To determine if JAK pathway inhibition can mitigate the negative effects of cellular senescence.

Main Methods:

  • Analysis of JAK pathway activation in senescent versus non-senescent cells.
  • Assessment of SASP component secretion following JAK pathway inhibition.
  • Evaluation of tissue function and age-related dysfunction markers after JAK inhibition.

Main Results:

  • The JAK pathway demonstrates heightened activation in senescent cells compared to non-senescent cells.
  • Inhibition of the JAK pathway effectively suppresses the SASP in senescent cells.
  • Targeting the JAK pathway alleviates age-related tissue dysfunction.

Conclusions:

  • The JAK pathway is a key regulator of the SASP in senescent cells.
  • JAK pathway inhibition represents a potential therapeutic strategy to combat age-related tissue dysfunction.
  • Targeting senescent cells via JAK inhibition may improve healthspan in aging populations.
Keywords:
Cellular senescenceFrailtyInsulin resistanceSenolytics

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.7K
Pharmacodynamics in Geriatric Patients: Effects of Age01:27

Pharmacodynamics in Geriatric Patients: Effects of Age

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...
311
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
9.1K
The Effect of Aging on Tissues01:19

The Effect of Aging on Tissues

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...
4.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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...
6.2K
Aging01:26

Aging

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...
967