Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock.

By R. Kondratov, A. Kondratova, V. Gorbacheva, Olena V. Vykhovanets, M. Antoch. Genes & Development, 2006

1,161 citations recorded by the source corpus.

Mice deficient in the circadian transcription factor BMAL1 (brain and muscle ARNT-like protein) have impaired circadian behavior and demonstrate loss of rhythmicity in the expression of target genes. Here we report that Bmal1(-/-) mice have reduced lifespans and display various symptoms of premature aging including sarcopenia, cataracts, less subcutaneous fat, organ shrinkage, and others. The early aging phenotype correlates with increased levels of reactive oxygen species in some tissues of the Bmal1(-/- )animals. These findings, together with data on CLOCK/BMAL1-dependent control of stress responses, may provide a mechanistic explanation for the early onset of age-related pathologies in the absence of BMAL1.

Subfields: Aging, Endocrine and Autonomic Systems, Physiology

View Paper: https://www.semanticscholar.org/paper/a2f5e8250adbcb6f9ad378319352b92879e9a5ff

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

1. M. McBurney
2. Danica Chen
3. L. Guarente
4. Paolo Sassone-Corsi
5. Saurabh Sahar
6. Yasukazu Nakahata
7. M. Kaluzová
8. D. Sinclair

In Endocrine and Autonomic Systems

1. Paolo Sassone-Corsi
2. L. Guarente
3. J. Hirayama
4. Saurabh Sahar
5. J. Takahashi

In Physiology

1. M. McBurney
2. Danica Chen
3. L. Guarente
4. Paolo Sassone-Corsi
5. Saurabh Sahar
6. Yasukazu Nakahata
7. M. Kaluzová
8. J. Hirayama

Citations in the corpus

• NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential (2020, background): “Thus, NAD(P)/NAD(P)H acts as an important modulator of cellular energetic status, enabling the reset of redox rhythmic and transcriptional oscillations based on metabolic signals.(254)”
• The NAD+-Dependent Deacetylase SIRT1 Modulates CLOCK-Mediated Chromatin Remodeling and Circadian Control (2008, background): “…of SIRT1 in the aging process (Oberdoerffer and Sinclair, 2007; Bishop and Guarente, 2007) is intriguingly paralleled by recent observations of early aging and age-related pathologies Cell 134, 329–340, July 25, 2008 ª2008 Elsevier Inc. 337 observed in BMAL1-deficient mice (Kondratov et al., 2006).”
• AMP-Activated Protein Kinase–Deficient Mice Are Resistant to the Metabolic Effects of Resveratrol (2009, methodology): “Certainly, converting muscle fiber to mitochondria-rich, slow-twitch fibers increases physical endurance (52).”