Nuclear envelope dysfunction and its contribution to the aging process.

Abstract:

:The nuclear envelope (NE) is the central organizing unit of the eukaryotic cell serving as a genome protective barrier and mechanotransduction interface between the cytoplasm and the nucleus. The NE is mainly composed of a nuclear lamina and a double membrane connected at specific points where the nuclear pore complexes (NPCs) form. Physiological aging might be generically defined as a functional decline across lifespan observed from the cellular to organismal level. Therefore, during aging and premature aging, several cellular alterations occur, including nuclear-specific changes, particularly, altered nuclear transport, increased genomic instability induced by DNA damage, and telomere attrition. Here, we highlight and discuss proteins associated with nuclear transport dysfunction induced by aging, particularly nucleoporins, nuclear transport factors, and lamins. Moreover, changes in the structure of chromatin and consequent heterochromatin rearrangement upon aging are discussed. These alterations correlate with NE dysfunction, particularly lamins' alterations. Finally, telomere attrition is addressed and correlated with altered levels of nuclear lamins and nuclear lamina-associated proteins. Overall, the identification of molecular mechanisms underlying NE dysfunction, including upstream and downstream events, which have yet to be unraveled, will be determinant not only to our understanding of several pathologies, but as here discussed, in the aging process.

journal_name

Aging Cell

journal_title

Aging cell

authors

Martins F,Sousa J,Pereira CD,da Cruz E Silva OAB,Rebelo S

doi

10.1111/acel.13143

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

e13143

issue

5

eissn

1474-9718

issn

1474-9726

journal_volume

19

pub_type

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