Universität zu Köln

da Silva, Paulo F. L., Ogrodnik, Mikolaj, Kucheryavenko, Olena, Glibert, Julien, Miwa, Satomi ORCID: 0000-0002-1239-1198, Cameron, Kerry, Ishaq, Abbas, Saretzki, Gabriele, Nagaraja-Grellscheid, Sushma, Nelson, Glyn ORCID: 0000-0002-1895-4772 and von Zglinicki, Thomas ORCID: 0000-0002-5939-0248 (2019). The bystander effect contributes to the accumulation of senescent cells in vivo. Aging Cell, 18 (1). HOBOKEN: WILEY. ISSN 1474-9726

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Abstract

Senescent cells accumulate with age in multiple tissues and may cause age-associated disease and functional decline. In vitro, senescent cells induce senescence in bystander cells. To see how important this bystander effect may be for accumulation of senescent cells in vivo, we xenotransplanted senescent cells into skeletal muscle and skin of immunocompromised NSG mice. 3 weeks after the last transplantation, mouse dermal fibroblasts and myofibres displayed multiple senescence markers in the vicinity of transplanted senescent cells, but not where non-senescent or no cells were injected. Adjacent to injected senescent cells, the magnitude of the bystander effect was similar to the increase in senescence markers in myofibres between 8 and 32 months of age. The age-associated increase of senescence markers in muscle correlated with fibre thinning, a widely used marker of muscle aging and sarcopenia. Senescent cell transplantation resulted in borderline induction of centrally nucleated fibres and no significant thinning, suggesting that myofibre aging might be a delayed consequence of senescence-like signalling. To assess the relative importance of the bystander effect versus cell-autonomous senescence, we compared senescent hepatocyte frequencies in livers of wild-type and NSG mice under ad libitum and dietary restricted feeding. This enabled us to approximate cell-autonomous and bystander-driven senescent cell accumulation as well as the impact of immunosurveillance separately. The results suggest a significant impact of the bystander effect for accumulation of senescent hepatocytes in liver and indicate that senostatic interventions like dietary restriction may act as senolytics in immunocompetent animals.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code da Silva, Paulo F. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ogrodnik, Mikolaj UNSPECIFIED UNSPECIFIED UNSPECIFIED Kucheryavenko, Olena UNSPECIFIED UNSPECIFIED UNSPECIFIED Glibert, Julien UNSPECIFIED UNSPECIFIED UNSPECIFIED Miwa, Satomi UNSPECIFIED orcid.org/0000-0002-1239-1198 UNSPECIFIED Cameron, Kerry UNSPECIFIED UNSPECIFIED UNSPECIFIED Ishaq, Abbas UNSPECIFIED UNSPECIFIED UNSPECIFIED Saretzki, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagaraja-Grellscheid, Sushma UNSPECIFIED UNSPECIFIED UNSPECIFIED Nelson, Glyn UNSPECIFIED orcid.org/0000-0002-1895-4772 UNSPECIFIED von Zglinicki, Thomas UNSPECIFIED orcid.org/0000-0002-5939-0248 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-157508
DOI:	10.1111/acel.12848
Journal or Publication Title:	Aging Cell
Volume:	18
Number:	1
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1474-9726
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA-DAMAGE RESPONSE; CELLULAR SENESCENCE; SKELETAL-MUSCLE; SECRETORY PHENOTYPE; IDENTIFICATION; MITOCHONDRIA; APOPTOSIS; DRIVEN; TISSUE; MICE Multiple languages Cell Biology; Geriatrics & Gerontology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15750