Related Experiment Video

Updated: Oct 20, 2025

Label-Free Imaging of Lipid Storage Dynamics in Caenorhabditis elegans using Stimulated Raman Scattering Microscopy
10:59

Label-Free Imaging of Lipid Storage Dynamics in Caenorhabditis elegans using Stimulated Raman Scattering Microscopy

Published on: May 28, 2021

4.4K

End-of-life targeted degradation of DAF-2 insulin/IGF-1 receptor promotes longevity free from growth-related

Richard Venz1, Tina Pekec2,3, Iskra Katic3

  • 1Eidgenössische Technische Hochschule Zürich, Department of Health Sciences and Technology, Institute of Translational Medicine, Schwerzenbach-Zürich, Switzerland.

Elife
|September 10, 2021
PubMed

Insights

Targeting insulin/IGF-1 signaling late in life can extend lifespan without negative effects. This study shows that reducing DAF-2 protein in old worms can double their remaining lifespan, offering a new aging intervention strategy.

Area of Science:

  • Gerontology
  • Molecular Biology
  • Genetics

Background:

  • Reducing insulin/insulin-like growth factor (IGF)-1 signaling (IIS) is a known lifespan-extending strategy across species.
  • The efficacy of IIS interventions late in life and their potential pathologies remain largely unexplored.

Purpose of the Study:

  • To investigate the effects of late-life interventions targeting IIS on lifespan and healthspan.
  • To develop a method for temporal and spatial control of IIS in aging organisms.

Main Methods:

  • Engineered a conditional depletion system (auxin-inducible degradation - AID) for the DAF-2 receptor in *Caenorhabditis elegans*.
  • Applied DAF-2 depletion at various life stages, including late adulthood and geriatric ages.
  • Assessed lifespan extension and adverse phenotypes associated with DAF-2 depletion.

Main Results:

  • AID-mediated DAF-2 depletion extended lifespan beyond that of existing *daf-2* mutants.
  • Early adulthood DAF-2 depletion caused adverse effects (growth retardation, reduced fertility).
  • Late-life or intestine-specific DAF-2 depletion extended lifespan without pathologies.
  • Geriatric DAF-2 depletion doubled the lifespan of aged worms.

Conclusions:

  • Temporal and spatial control of IIS is crucial for effective lifespan extension without detrimental side effects.
  • Late-life interventions targeting IIS, even near the end of lifespan, can significantly slow aging.
  • This study provides a proof-of-concept for developing late-life aging interventions.
Keywords:
C. elegansDAF-2agingauxindauerdegrondevelopmental biologydiet

More Related Videos

The Replica Set Method: A High-throughput Approach to Quantitatively Measure Caenorhabditis elegans Lifespan11:58

The Replica Set Method: A High-throughput Approach to Quantitatively Measure Caenorhabditis elegans Lifespan

Published on: June 29, 2018

9.6K
Lipid Supplementation for Longevity and Gene Transcriptional Analysis in Caenorhabditis elegans07:25

Lipid Supplementation for Longevity and Gene Transcriptional Analysis in Caenorhabditis elegans

Published on: December 9, 2022

1.7K

Related Concept Videos

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...
4.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
Replicative Cell Senescence02:15

Replicative Cell Senescence

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...
3.9K
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.7K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.7K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.8K