Ca2+/calmodulin signaling in organismal aging and cellular senescence: Impact on human diseases

Martin W. Berchtold; Antonio Villalobo

doi:10.1016/j.bbadis.2024.167583

Ca²⁺/calmodulin signaling in organismal aging and cellular senescence: Impact on human diseases

Martin W. Berchtold^*, Antonio Villalobo

^*Corresponding author af dette arbejde

Cellebiologi og Fysiologi

Publikation: Bidrag til tidsskrift › Review › Forskning › peer review

1 Citationer (Scopus)

Abstract

Molecular mechanisms of aging processes at the level of organisms and cells are in the focus of a large number of research laboratories. This research culminated in recent breakthroughs, which contributed to the better understanding of the natural aging process and aging associated malfunctions leading to age-related diseases. Ca2+ in connection with its master intracellular sensor protein calmodulin (CaM) regulates a plethora of crucial cellular processes orchestrating a wide range of signaling processes. This review focuses on the involvement of Ca2+/CaM in cellular mechanisms, which are associated with normal aging, as well as playing a role in the development of diseases connected with signaling processes during aging. We specifically highlight processes that involve inactivation of proteins, which take part in Ca2+/CaM regulatory systems by oxygen or nitrogen free radical species, during organismal aging and cellular senescence. As examples of organs where aging processes have recently been investigated, we chose to review the literature on molecular aging processes with involvement of Ca2+/CaM in heart and neuronal diseases, as well as in cancer and metabolic diseases, all deeply affected by aging. In addition, this article focuses on cellular senescence, a mechanism that may contribute to aging processes and therefore has been proposed as a target to interfere with the progression of age-associated diseases.

Originalsprog	Engelsk
Artikelnummer	167583
Tidsskrift	Biochimica et Biophysica Acta - Molecular Basis of Disease
Vol/bind	1871
Udgave nummer	2
Antal sider	21
ISSN	0925-4439
DOI	https://doi.org/10.1016/j.bbadis.2024.167583
Status	Udgivet - 2025

Bibliografisk note

Funding Information:
This work was funded by grants to MWB from the Danish Research Council (DFF-4004-00560), the Wedell Wedellsborg Foundation and the Candys Foundation, Denmark. Work in the former lab of AV at the Instituto de Investigaciones Biom\u00E9dicas, Consejo Superior de Investigaciones Cient\u00EDficas-Universidad Aut\u00F3noma de Madrid was funded by grants from the following agencies: Fondo de Investigaciones Sanitarias de la Seguridad Social, Direcci\u00F3n General de Investigaci\u00F3n Cient\u00EDfica y Tecnol\u00F3gica, Comisi\u00F3n Interministerial de Ciencia y Tecnolog\u00EDa \u2014 Plan Nacional de I + D + I, Agencia Espa\u00F1ola de Cooperaci\u00F3n Internacional, Ministerio de Educaci\u00F3n y Cultura, Fundaci\u00F3n Mapfre Medicina, Consejer\u00EDa de Educaci\u00F3n de la Comunidad de Madrid, Spain; and the European Commission. We thank Alberto Bengur\u00EDa, from the Spanish National Centre for Cardiovascular Research, Madrid Spain, and Juan Alcalde from the United Kingdom Dementia Research Institute at King's College London, United Kingdom, for reading some sections of the review and providing valuable comments and suggestions. Mads Munk, University of Copenhagen, Department of Biology, is acknowledged for providing the microscopic pictures of wild type and CaM knock out senescent HeLa cells. We are grateful for the excellent work done by the reviewers of our paper.

Funding Information:
This work was funded by grants to MWB from the Danish Research Council ( DFF-4004-00560 ), the Wedell Wedellsborg Foundation and the Candys Foundation , Denmark. Work in the former lab of AV at the Instituto de Investigaciones Biom\u00E9dicas, Consejo Superior de Investigaciones Cient\u00EDficas-Universidad Aut\u00F3noma de Madrid was funded by grants from the following agencies: Fondo de Investigaciones Sanitarias de la Seguridad Social , Direcci\u00F3n General de Investigaci\u00F3n Cient\u00EDfica y Tecnol\u00F3gica , Comisi\u00F3n Interministerial de Ciencia y Tecnolog\u00EDa \u2014 Plan Nacional de I\u202F+\u202FD\u202F+\u202FI, Agencia Espa\u00F1ola de Cooperaci\u00F3n Internacional , Ministerio de Educaci\u00F3n y Cultura , Fundaci\u00F3n Mapfre Medicina , Consejer\u00EDa de Educaci\u00F3n de la Comunidad de Madrid , Spain; and the European Commission . We thank Alberto Bengur\u00EDa, from the Spanish National Centre for Cardiovascular Research, Madrid Spain, and Juan Alcalde from the United Kingdom Dementia Research Institute at King's College London, United Kingdom, for reading some sections of the review and providing valuable comments and suggestions. Mads Munk, University of Copenhagen, Department of Biology, is acknowledged for providing the microscopic pictures of wild type and CaM knock out senescent HeLa cells. We are grateful for the excellent work done by the reviewers of our paper.

Publisher Copyright:
© 2024 Elsevier B.V.

Adgang til dokumentet

10.1016/j.bbadis.2024.167583

Citationsformater

@article{3c8ec459fc614f8db30012f933e1d646,

title = "Ca2+/calmodulin signaling in organismal aging and cellular senescence: Impact on human diseases",

abstract = "Molecular mechanisms of aging processes at the level of organisms and cells are in the focus of a large number of research laboratories. This research culminated in recent breakthroughs, which contributed to the better understanding of the natural aging process and aging associated malfunctions leading to age-related diseases. Ca2+ in connection with its master intracellular sensor protein calmodulin (CaM) regulates a plethora of crucial cellular processes orchestrating a wide range of signaling processes. This review focuses on the involvement of Ca2+/CaM in cellular mechanisms, which are associated with normal aging, as well as playing a role in the development of diseases connected with signaling processes during aging. We specifically highlight processes that involve inactivation of proteins, which take part in Ca2+/CaM regulatory systems by oxygen or nitrogen free radical species, during organismal aging and cellular senescence. As examples of organs where aging processes have recently been investigated, we chose to review the literature on molecular aging processes with involvement of Ca2+/CaM in heart and neuronal diseases, as well as in cancer and metabolic diseases, all deeply affected by aging. In addition, this article focuses on cellular senescence, a mechanism that may contribute to aging processes and therefore has been proposed as a target to interfere with the progression of age-associated diseases.",

keywords = "Aging, Calmodulin, Cellular senescence, Disease, Neurodegeneration",

author = "Berchtold, {Martin W.} and Antonio Villalobo",

note = "Publisher Copyright: {\textcopyright} 2024 Elsevier B.V.",

year = "2025",

doi = "10.1016/j.bbadis.2024.167583",

language = "English",

volume = "1871",

journal = "B B A - Molecular Basis of Disease",

issn = "0925-4439",

publisher = "Elsevier",

number = "2",

}

TY - JOUR

T1 - Ca2+/calmodulin signaling in organismal aging and cellular senescence

T2 - Impact on human diseases

AU - Berchtold, Martin W.

AU - Villalobo, Antonio

PY - 2025

Y1 - 2025

N2 - Molecular mechanisms of aging processes at the level of organisms and cells are in the focus of a large number of research laboratories. This research culminated in recent breakthroughs, which contributed to the better understanding of the natural aging process and aging associated malfunctions leading to age-related diseases. Ca2+ in connection with its master intracellular sensor protein calmodulin (CaM) regulates a plethora of crucial cellular processes orchestrating a wide range of signaling processes. This review focuses on the involvement of Ca2+/CaM in cellular mechanisms, which are associated with normal aging, as well as playing a role in the development of diseases connected with signaling processes during aging. We specifically highlight processes that involve inactivation of proteins, which take part in Ca2+/CaM regulatory systems by oxygen or nitrogen free radical species, during organismal aging and cellular senescence. As examples of organs where aging processes have recently been investigated, we chose to review the literature on molecular aging processes with involvement of Ca2+/CaM in heart and neuronal diseases, as well as in cancer and metabolic diseases, all deeply affected by aging. In addition, this article focuses on cellular senescence, a mechanism that may contribute to aging processes and therefore has been proposed as a target to interfere with the progression of age-associated diseases.

AB - Molecular mechanisms of aging processes at the level of organisms and cells are in the focus of a large number of research laboratories. This research culminated in recent breakthroughs, which contributed to the better understanding of the natural aging process and aging associated malfunctions leading to age-related diseases. Ca2+ in connection with its master intracellular sensor protein calmodulin (CaM) regulates a plethora of crucial cellular processes orchestrating a wide range of signaling processes. This review focuses on the involvement of Ca2+/CaM in cellular mechanisms, which are associated with normal aging, as well as playing a role in the development of diseases connected with signaling processes during aging. We specifically highlight processes that involve inactivation of proteins, which take part in Ca2+/CaM regulatory systems by oxygen or nitrogen free radical species, during organismal aging and cellular senescence. As examples of organs where aging processes have recently been investigated, we chose to review the literature on molecular aging processes with involvement of Ca2+/CaM in heart and neuronal diseases, as well as in cancer and metabolic diseases, all deeply affected by aging. In addition, this article focuses on cellular senescence, a mechanism that may contribute to aging processes and therefore has been proposed as a target to interfere with the progression of age-associated diseases.

KW - Aging

KW - Calmodulin

KW - Cellular senescence

KW - Disease

KW - Neurodegeneration

U2 - 10.1016/j.bbadis.2024.167583

DO - 10.1016/j.bbadis.2024.167583

M3 - Review

C2 - 39579800

AN - SCOPUS:85209769377

VL - 1871

JO - B B A - Molecular Basis of Disease

JF - B B A - Molecular Basis of Disease

SN - 0925-4439

IS - 2

M1 - 167583

ER -