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Are there roles for brain cell senescence in aging and neurodegenerative disorders?

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Abstract

The term cellular senescence was introduced more than five decades ago to describe the state of growth arrest observed in aging cells. Since this initial discovery, the phenotypes associated with cellular senescence have expanded beyond growth arrest to include alterations in cellular metabolism, secreted cytokines, epigenetic regulation and protein expression. Recently, senescence has been shown to play an important role in vivo not only in relation to aging, but also during embryonic development. Thus, cellular senescence serves different purposes and comprises a wide range of distinct phenotypes across multiple cell types. Whether all cell types, including post-mitotic neurons, are capable of entering into a senescent state remains unclear. In this review we examine recent data that suggest that cellular senescence plays a role in brain aging and, notably, may not be limited to glia but also neurons. We suggest that there is a high level of similarity between some of the pathological changes that occur in the brain in Alzheimer’s and Parkinson’s diseases and those phenotypes observed in cellular senescence, leading us to propose that neurons and glia can exhibit hallmarks of senescence previously documented in peripheral tissues.

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Abbreviations

Aβ:

αmyloid β-peptide

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

ATM:

Ataxia telangiectasia mutated

ATR:

Ataxia telangiectasia and Rad3-related

β-gal:

Β-galactosidase

CGNs:

Cerebellar granule neurons

CNS:

Central nervous system

CS:

Cellular senescence

CSF:

Cerebrospinal fluid

DDR:

DNA damage response

Ecrg4:

Esophageal cancer-related gene 4

FTD:

Frontotemporal dementia

HD:

Huntington’s disease

LTP:

Long-term potentiation

MiRNA:

Microrna

NSCs:

Neural stem cells

OIS:

Oncogene-induced senescence

OPCs:

Oligodendrocyte precursor cells

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

RS:

Replicative senescence

SA β-gal:

Senescence-associated β-gal

SAHF:

Senescence-associated heterochromatic foci

SASP:

Senescence-associated secretory phenotype

SIPS:

Stress induced replicative senescence

SIR:

Senescence-associated inflammatory response

TGFβ:

Transforming growth factor β

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Acknowledgments

This research was supported by the Intramural Research Program of the NIH, National Institute on Aging.

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  1. Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, 21224, USA

    Florence C. C. Tan, Emmette R. Hutchison, Erez Eitan & Mark P. Mattson

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  1. Florence C. C. Tan
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  2. Emmette R. Hutchison
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Tan, F.C.C., Hutchison, E.R., Eitan, E. et al. Are there roles for brain cell senescence in aging and neurodegenerative disorders?. Biogerontology 15, 643–660 (2014). https://doi.org/10.1007/s10522-014-9532-1

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