Where Ideas Grow

Ageing and Aneuploidy

ABOUT

Ageing is a biological process characterized by the progressive deterioration of physiological functions known to be the main risk factor for chronic diseases and declining health. Given the exponential increase of the elderly population and its substantial burden on the health care system, the research in ageing biology becomes a priority. There has been an emerging connection between ageing and aneuploidy, an aberrant number of chromosomes, even though the molecular mechanisms remain largely unknown. Since 2015, the Ageing & Aneuploidy group has been dedicated to high-profile research on the mechanisms of cell cycle dysregulation and genomic instability contributing to ageing and age-related diseases. Presently, the group applies interdisciplinary approaches to address how regulated instruction of cell cycle fitness and genomic stability decelerates senescence in cellular and mouse models of Down syndrome, progeria and ageing.

 

RESEARCH

Two major contributions arose from the group’s expertise in combining high-resolution live-cell imaging with advanced molecular/cellular biology techniques to characterize phenotypes of unique cellular models, human trisomic amniocytes [Elife 2015, Sci Rep 2016] and elderly dermal fibroblasts [Nat Commun 2018, Embo Rep 2020]. These studies unveiled chromosomal instability (CIN) as a hallmark in both aneuploid and aged cells. Moreover, we disclosed genetic and pharmacological modulations of ageing-associated CIN as able to delay the senescence pro-inflammatory response. These findings paved the way to our current and future research goals, aiming to deepen the understanding of ageing mechanisms and to test new schemes of healthspan extension in animal models. The lab uses omics approaches and functional assays to measure cellular and tissue ageing.

Abnormal chromosome segregation during cell division of a human elderly dermal fibroblast. Immunofluorescence image of the anaphase stage of mitosis, with sister chromatids (blue/purple) being pulled into opposite poles by the spindle microtubules (green). Lagging chromosome fragments (purple) in th

Team

Selected Publications

Ferreira F.J., Carvalho L., Logarinho E., Bessa J.,
Foxm1 modulates cell non-autonomous response in zebrafish skeletal muscle homeostasis. Cells10(5):, 2021. [Journal: Article] [CI: 2] [IF: 7,7]
DOI: 10.3390/cells10051241 SCOPUS: 85107456993

Vaz S., Ferreira F.J., Macedo J.C., Leor G., Ben-David U., Bessa J., Logarinho E.,
FOXM1 repression increases mitotic death upon antimitotic chemotherapy through BMF upregulation. Cell Death and Disease12(6):, 2021. [Journal: Article] [CI: 3] [IF: 9,7]
DOI: 10.1038/s41419-021-03822-5 SCOPUS: 85106857863

Barroso-Vilares M., Macedo J.C., Reis M., Warren J.D., Compton D., Logarinho E.,
Small-molecule inhibition of aging-associated chromosomal instability delays cellular senescence. EMBO Reports21(5):, 2020. [Journal: Article] [CI: 15] [IF: 8,8]
DOI: 10.15252/embr.201949248 SCOPUS: 85081638234

Pereira S.M., Ribeiro R., Logarinho E.,
Approaches towards longevity: Reprogramming, senolysis, and improved mitotic competence as anti-aging therapies. International Journal of Molecular Sciences20(4):, 2019. [Journal: Review] [CI: 15] [IF: 4,6]
DOI: 10.3390/ijms20040938 SCOPUS: 85062013237

Barroso-Vilares M., Logarinho E.,
Chromosomal instability and pro-inflammatory response in aging. Mechanisms of Ageing and Development182:, 2019. [Journal: Review] [CI: 12] [IF: 4,3]
DOI: 10.1016/j.mad.2019.111118 SCOPUS: 85065928704

Pinho M., Macedo J.C., Logarinho E., Pereira P.S.,
NoL12 repression induces nucleolar stress-driven cellular senescence and is associated with normative aging. Molecular and Cellular Biology39(12):, 2019. [Journal: Article] [CI: 8] [IF: 3,6]
DOI: 10.1128/MCB.00099-19 SCOPUS: 85066485467

Macedo J.C., Vaz S., Bakker B., Ribeiro R., Bakker P.L., Escandell J.M., Ferreira M.G., Medema R., Foijer F., Logarinho E.,
FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence. Nature Communications9(1):, 2018. [Journal: Article] [CI: 54] [IF: 11,9]
DOI: 10.1038/s41467-018-05258-6 SCOPUS: 85050593345

Macedo J.C., Vaz S., Logarinho E.,
Mitotic dysfunction associated with aging hallmarks. Advances in Experimental Medicine and Biology1002:153-188, 2017. [Book Series: Book Chapter] [CI: 20] [IF: 1,8]
DOI: 10.1007/978-3-319-57127-0_7 SCOPUS: 85020653311

Rutledge S.D., Douglas T.A., Nicholson J.M., Vila-Casadesús M., Kantzler C.L., Wangsa D., Barroso-Vilares M., Kale S.D., Logarinho E., Cimini D.,
Selective advantage of trisomic human cells cultured in non-standard conditions. Scientific Reports6:, 2016. [Journal: Article] [CI: 58] [IF: 4,3]
DOI: 10.1038/srep22828 SCOPUS: 84959009777

Nicholson J.M., Macedo J.C., Mattingly A.J., Wangsa D., Camps J., Lima V., Gomes A.M., Dória S., Ried T., Logarinho E., Cimini D.,
Chromosome mis-segregation and cytokinesis failure in trisomic human cells. eLife4(MAY):, 2015. [Journal: Article] [CI: 66] [IF: 8,3]
DOI: 10.7554/eLife.05068 SCOPUS: 84930649727

Ongoing Projects

Small-molecule modulation of aging-associated DNA damage and epigenetic erosion
Reference: PTDC/MED-OUT/2747/2020
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-FEB-21 to 31-JAN-24
Feedback regulation behind age-associated cell cycle slow down as a potencial anti-aging target
Reference: EXPL/BIA-CEL/0446/2021
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-JAN-22 to 30-JUN-23
Small-molecule inhibition of genomic instability-driven senescence in Down syndrome
Reference: Project 2094 - 2021
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Jerome Lejeune Foundation
From 01-JAN-22 to 31-DEC-23