Naturally occurring p16Ink4a-positive cells shorten healthy lifespan

Overview of attention for article published in Nature, February 2016
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

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mendeley
520 Mendeley
citeulike
5 CiteULike
Title
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Published in
Nature, February 2016
DOI 10.1038/nature16932
Pubmed ID
Authors

Darren J. Baker, Bennett G. Childs, Matej Durik, Melinde E. Wijers, Cynthia J. Sieben, Jian Zhong, Rachel A. Saltness, Karthik B. Jeganathan, Grace Casaclang Verzosa, Abdulmohammad Pezeshki, Khashayarsha Khazaie, Jordan D. Miller, Jan M. van Deursen, Baker, Darren J, Childs, Bennett G, Durik, Matej, Wijers, Melinde E, Sieben, Cynthia J, Zhong, Jian, A Saltness, Rachel, Jeganathan, Karthik B, Verzosa, Grace Casaclang, Pezeshki, Abdulmohammad, Khazaie, Khashayarsha, Miller, Jordan D, van Deursen, Jan M, Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, Saltness RA, Jeganathan KB, Verzosa GC, Pezeshki A, Khazaie K, Miller JD, van Deursen JM, Rachel Saltness, Grace C. Versoza, Abdul-Mohammad Pezeshki

Abstract

Cellular senescence, a stress-induced irreversible growth arrest often characterized by expression of p16(Ink4a) (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16(Ink4a)-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16(Ink4a)-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16(Ink4a)-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.

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Mendeley readers

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Geographical breakdown

Country Count As %
United States 11 2%
United Kingdom 5 <1%
Germany 3 <1%
Spain 3 <1%
France 2 <1%
China 2 <1%
Russian Federation 2 <1%
Japan 2 <1%
Chile 1 <1%
Other 11 2%
Unknown 478 92%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 152 29%
Researcher 114 22%
Student > Master 76 15%
Student > Bachelor 53 10%
Professor > Associate Professor 33 6%
Other 92 18%
Readers by discipline Count As %
Agricultural and Biological Sciences 276 53%
Biochemistry, Genetics and Molecular Biology 124 24%
Medicine and Dentistry 64 12%
Neuroscience 12 2%
Chemistry 8 2%
Other 36 7%

Attention Score in Context

This research output has an Altmetric Attention Score of 1831. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 March 2017.
All research outputs
#295
of 7,449,206 outputs
Outputs from Nature
#88
of 45,548 outputs
Outputs of similar age
#28
of 323,882 outputs
Outputs of similar age from Nature
#8
of 966 outputs
Altmetric has tracked 7,449,206 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 45,548 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 70.0. This one has done particularly well, scoring higher than 99% of its peers.
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We're also able to compare this research output to 966 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.