Kelli Pointer

Publications (2)39.96 Total impact

• Article: Deviation of innate circadian period from 24 h reduces longevity in mice.

  Sergiy Libert, Michael S Bonkowski, Kelli Pointer, Scott D Pletcher, Leonard Guarente
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  ABSTRACT: The variation of individual life spans, even in highly inbred cohorts of animals and under strictly controlled environmental conditions, is substantial and not well understood. This variation in part could be due to epigenetic variation, which later affects the animal's physiology and ultimately longevity. Identification of the physiological properties that impact health and life span is crucial for longevity research and the development of anti-aging therapies. Here, we measured individual circadian and metabolic characteristics in a cohort of inbred F1 hybrid mice and correlated these parameters to their life spans. We found that mice with innate circadian periods close to 24 h (revealed during 30 days of housing in total darkness) enjoyed nearly 20% longer life spans than their littermates, which had shorter or longer innate circadian periods. These findings show that maintenance of a 24-h intrinsic circadian period is a positive predictor of longevity. Our data suggest that circadian period may be used to predict individual longevity and that processes that control innate circadian period affect aging.
  Aging cell 06/2012; 11(5):794-800. · 7.55 Impact Factor
• Article: SIRT1 activates MAO-A in the brain to mediate anxiety and exploratory drive.

  Sergiy Libert, Kelli Pointer, Eric L Bell, Abhirup Das, Dena E Cohen, John M Asara, Karen Kapur, Sven Bergmann, Martin Preisig, Takeshi Otowa, Kenneth S Kendler, Xiangning Chen, John M Hettema, Edwin J van den Oord, Justin P Rubio, Leonard Guarente
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  ABSTRACT: SIRT1 is a NAD(+)-dependent deacetylase that governs a number of genetic programs to cope with changes in the nutritional status of cells and organisms. Behavioral responses to food abundance are important for the survival of higher animals. Here we used mice with increased or decreased brain SIRT1 to show that this sirtuin regulates anxiety and exploratory drive by activating transcription of the gene encoding the monoamine oxidase A (MAO-A) to reduce serotonin levels in the brain. Indeed, treating animals with MAO-A inhibitors or selective serotonin reuptake inhibitors (SSRIs) normalized anxiety differences between wild-type and mutant animals. SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter. Both common and rare variations in the SIRT1 gene were shown to be associated with risk of anxiety in human population samples. Together these data indicate that SIRT1 mediates levels of anxiety, and this regulation may be adaptive in a changing environment of food availability.
  Cell 12/2011; 147(7):1459-72. · 32.40 Impact Factor