Lamin B1 decline underlies age‐related loss of adult hippocampal neurogenesis
Tracy A Bedrosian,
Judith Houtman,
Juan Sebastian Eguiguren,
Saeed Ghassemzadeh,
Nicole Rund,
Nicole M Novaresi,
Lauren Hu,
Sarah L. Parylak,
Ahmet M Denli, et al.
Neurogenesis in the adult hippocampus declines with age, a process that has been implicated in cognitive and emotional impairments. However, the mechanisms underlying this decline have remained elusive. Here, we show that the age‐dependent downregulation of lamin B1, one of the nuclear lamins in adult neural stem/progenitor cells (ANSPCs), underlies age‐related alterations in adult hippocampal neurogenesis. Our results indicate that higher levels of lamin B1 in ANSPCs safeguard against premature differentiation and regulate the maintenance of ANSPCs. However, the level of lamin B1 in ANSPCs declines during aging. Precocious loss of lamin B1 in ANSPCs transiently promotes neurogenesis but eventually depletes it. Furthermore, the reduction of lamin B1 in ANSPCs recapitulates age‐related anxiety‐like behavior in mice. Our results indicate that the decline in lamin B1 underlies stem cell aging and impacts the homeostasis of adult neurogenesis and mood regulation.
When function follows form: Nuclear compartment structure and the epigenetic landscape of the aging neuron
Johannes C.M. Schlachetzki,
Tomohisha Toda,
Jerome Mertens
The human brain is affected by cellular aging. Neurons are primarily generated during embryogenesis and early life with a limited capacity for renewal and replacement, making them some of the oldest cells in the human body. Our present understanding of neurodegenerative diseases points towards advanced neuronal age as a prerequisite for the development of these disorders. While significant progress has been made in understanding the relationship between aging and neurological disease, it will be essential to delve further into the molecular mechanisms of neuronal aging in order to develop therapeutic interventions targeting age-related brain dysfunction. In this mini review, we highlight recent findings on the relationship between the aging of nuclear structures and changes in the epigenetic landscape during neuronal aging and disease.
Contact
Research Group Tomohisa Toda
Max-Planck-Zentrum für Physik und Medizin Kussmaulallee 2 91054 Erlangen, Germany
