Birkisdottir, Maria B., Jaarsma, Dick ORCID: 0000-0002-0519-2940, Brandt, Renata M. C., Barnhoorn, Sander, van Vliet, Nicole, Imholz, Sandra, van Oostrom, Conny T., Nagarajah, Bhawani, Portilla Fernandez, Eliana, Roks, Anton J. M., Elgersma, Ype, van Steeg, Harry, Ferreira, Jose A., Pennings, Jeroen L. A., Hoeijmakers, Jan H. J., Vermeij, Wilbert P. and Dolle, Martijn E. T. (2021). Unlike dietary restriction, rapamycin fails to extend lifespan and reduce transcription stress in progeroid DNA repair-deficient mice. Aging Cell, 20 (2). HOBOKEN: WILEY. ISSN 1474-9726

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Abstract

Dietary restriction (DR) and rapamycin extend healthspan and life span across multiple species. We have recently shown that DR in progeroid DNA repair-deficient mice dramatically extended healthspan and trippled life span. Here, we show that rapamycin, while significantly lowering mTOR signaling, failed to improve life span nor healthspan of DNA repair-deficient Ercc1( increment /-) mice, contrary to DR tested in parallel. Rapamycin interventions focusing on dosage, gender, and timing all were unable to alter life span. Even genetically modifying mTOR signaling failed to increase life span of DNA repair-deficient mice. The absence of effects by rapamycin on P53 in brain and transcription stress in liver is in sharp contrast with results obtained by DR, and appoints reducing DNA damage and transcription stress as an important mode of action of DR, lacking by rapamycin. Together, this indicates that mTOR inhibition does not mediate the beneficial effects of DR in progeroid mice, revealing that DR and rapamycin strongly differ in their modes of action.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Birkisdottir, Maria B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jaarsma, DickUNSPECIFIEDorcid.org/0000-0002-0519-2940UNSPECIFIED
Brandt, Renata M. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barnhoorn, SanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Vliet, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imholz, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Oostrom, Conny T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nagarajah, BhawaniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Portilla Fernandez, ElianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roks, Anton J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elgersma, YpeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Steeg, HarryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferreira, Jose A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pennings, Jeroen L. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoeijmakers, Jan H. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vermeij, Wilbert P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dolle, Martijn E. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-582539
DOI: 10.1111/acel.13302
Journal or Publication Title: Aging Cell
Volume: 20
Number: 2
Date: 2021
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1474-9726
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Cell Biology; Geriatrics & GerontologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/58253

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