Related Experiment Video

Updated: Apr 20, 2026

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

10.9K

Linking DNA damage, NAD(+)/SIRT1, and aging

Leonard Guarente1

  • 1Novartis Professor of Biology, Director of the Glenn Labs for the Science of Aging, and Affiliate of the Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA.

Cell Metabolism
|December 3, 2014
PubMed

Insights

DNA damage repair defects cause premature aging. Increasing NAD(+) levels can reverse Sirt1 inactivation and mitochondrial issues in Cockayne Syndrome B, linked to PARP activity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Defects in DNA damage repair (DDR) pathways are linked to premature aging syndromes.
  • Cockayne Syndrome B (CSB) is a rare genetic disorder characterized by features of premature aging.
  • Nuclear NAD(+) depletion by Poly(ADP-ribose) polymerase (PARP) is implicated in CSB pathogenesis.

Purpose of the Study:

  • To investigate the therapeutic potential of NAD(+) supplementation in CSB.
  • To explore the impact of NAD(+) restoration on Sirt1 activity and mitochondrial function in CSB.

Main Methods:

  • Utilized a mouse model of Cockayne Syndrome B.
  • Administered NAD(+) precursors to CSB mice.
  • Assessed Sirt1 activity, mitochondrial respiration, and markers of aging.

Main Results:

  • Increased NAD(+) levels in CSB mice reversed Sirt1 inactivation.
  • NAD(+) supplementation ameliorated mitochondrial defects in CSB.
  • Restored mitochondrial function correlated with reduced signs of premature aging.

Conclusions:

  • NAD(+) replenishment is a promising therapeutic strategy for Cockayne Syndrome B.
  • Targeting NAD(+) metabolism may offer a novel approach to treating premature aging disorders associated with DDR defects.

More Related Videos

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

4.2K
Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

8.8K

Related Concept Videos

Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
6.0K
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
42.9K
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

14.1K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.4K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.4K
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
35.6K