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 behind age-associated aneuploidy remain largely unknown. We are investigating the link between ageing and loss of mitotic fidelity, which could support the correlation between ageing and aneuploidy seen over the past decades. Moreover, we are studying the impact of aneuploidy in cellular ageing. Our working hypothesis is that there is a positive feedback regulation between ageing and aneuploidy, and that modulation of mitotic fidelity and aneuploidy is a potential means to ameliorate healthy lifespan. In addition, we are establishing new methodologies to accurately measure aneuploidy and determine chromosome-specific mis-segregation rates in both ageing and aneuploidy conditions. Finally, we are exploring the molecular signatures of ageing and aneuploidy for their implications in cancer and ageing therapies.

 

RESEARCH

The lab uses human primary fibroblasts and induced pluripotent stem cells to study cellular phenotypes associated with normative ageing, premature aging diseases and aneuploidy. In addition, we use the mouse model to study organismal aging and test new schemes of lifespan extension. The lab has strong expertise in cell biological and molecular approaches, in particular advanced time-lapse imaging, image-based quantitative assays, lentiviral technology, CRISPR-Cas9 gene editing and transcriptomics, which are being used to measure and/or manipulate age/aneuploidy-associated cellular phenotypes such as chromosomal instability, proteotoxic stress, epigenetic changes and senescence.

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
Selected Publications
Approaches towards Longevity: Reprogramming, Senolysis, and Improved Mitotic Competence as Anti-Aging Therapies. International Journal of Molecular Sciences20(4):, 2019. [Journal: Review] [IF: 3,7 (*)]
DOI: 10.3390/ijms20040938 SCOPUS: 85062013237

FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence. Nature Communications9(1):, 2018. [Journal: Article] [CI: 1] [IF: 12,4 (*)]
DOI: 10.1038/s41467-018-05258-6 SCOPUS: 85050593345

Mitotic dysfunction associated with aging hallmarks. Advances in Experimental Medicine and Biology1002:153-188, 2017. [Book Series: Chapter] [CI: 4] [IF: 1,8]
DOI: 10.1007/978-3-319-57127-0_7 SCOPUS: 85020653311

Selective advantage of trisomic human cells cultured in non-standard conditions. Scientific Reports6:, 2016. [Journal: Article] [CI: 22] [IF: 4,3]
DOI: 10.1038/srep22828 SCOPUS: 84959009777

Chromosome mis-segregation and cytokinesis failure in trisomic human cells. eLife4(MAY):, 2015. [Journal: Article] [CI: 36] [IF: 8,3]
DOI: 10.7554/eLife.05068 SCOPUS: 84930649727