Genetic mechanisms of ageing - Maria Eriksson
Our research concerns the genetic mechanisms that contribute to age-related decline of tissues and the development of age-associated disease. We use modern genomic technologies to identify genetic variations, and conditional in vivo models to dissect the functional significance of the variants discovered.
When we age, our tissues are characterised by a progressive loss of tissue function and regenerative capacity, which limits our physical performance and general health. The purpose of our research is to increase the knowledge about specific genetic and molecular factors that influence the onset of age-related diseases and affect health and disease. Advances in genomic technologies have made it possible to analyse somatic mutations in the whole genome of human cells and show that all cells accumulate mutations during development and ageing. This ongoing mutagenic process results in a tissue composed of cells with different genetic makeups, and is referred to as somatic mosaicism.
The specific aims include the development of a genetic atlas of somatic mutations across various cells of the human body. This atlas helps us to improve the current understanding of genetic events in cancer development and age-associated diseases, and to better comprehend the mutational processes that lead to differences in the somatic mutation landscape in different cells. Our results may also contribute to the development of therapies that could counteract the propagation of somatic mutagenesis, for example by the activation of DNA repair. Our most recent results indicate that the underlying mechanism responsible for age-related somatic mutagenesis, across most tissues, is the gradual loss of efficiency of DNA repair systems with ageing (Franco, Helgadottir et al., 2019).
Other projects in the lab include the study of the very rare premature ageing disorder Hutchinson-Gilford Progeria Syndrome (HGPS, progeria) and the development of novel treatment strategies. HGPS affects one in 18 million individuals and is caused by a de novo point mutation in the lamin A gene, LMNA c.1824C>T, leading to mis-splicing and production of a truncated lamin A protein named progerin. Children show typical symptoms of accelerated ageing and die in their teens due to accelerated atherosclerosis and cardiovascular disease. The underlying pathomechanisms remain unclear andclinical trials have shown only limited success.
The impact of our studies may be beneficial for ageing and promote healthy ageing,as well as encouraging the identification of novel treatments that alleviate age-associated diseases.
News from the group
Base Editing in Progeria
Kim J.-S. and Eriksson M
N Engl J Med 2021; 384:1364-1366
Splice-inhibition therapy targets progeria.
Revêchon G, Whisenant D, Eriksson M
Nat Med 2021 03;27(3):377-379
Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type.
Franco I, Helgadottir HT, Moggio A, Larsson M, Vrtačnik P, Johansson A, Norgren N, Lundin P, Mas-Ponte D, Nordström J, Lundgren T, Stenvinkel P, Wennberg L, Supek F, Eriksson M
Genome Biol 2019 12;20(1):285
Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson-Gilford Progeria Syndrome.
Aguado J, Sola-Carvajal A, Cancila V, Revêchon G, Ong PF, Jones-Weinert CW, Wallén Arzt E, Lattanzi G, Dreesen O, Tripodo C, Rossiello F, Eriksson M, d'Adda di Fagagna F.
Nat Commun 2019 11;10(1):4990
Analysis of somatic mutations identifies signs of selection during in vitro aging of primary dermal fibroblasts.
Narisu N, Rothwell R, Vrtačnik P, Rodríguez S, Didion J, Zöllner S, Erdos MR, Collins FS, Eriksson M.
Aging Cell 2019 12;18(6):e13010
Endothelial progerin expression causes cardiovascular pathology through an impaired mechanoresponse.
Osmanagic-Myers S, Kiss A, Manakanatas C, Hamza O, Sedlmayer F, Szabo PL, Fischer I, Fichtinger P, Podesser BK, Eriksson M, Foisner R.
J Clin Invest 2019 02;129(2):531-545
Healthy skeletal muscle aging: The role of satellite cells, somatic mutations and exercise.
Franco I, Fernandez-Gonzalo R, Vrtačnik P, Lundberg TR, Eriksson M, Gustafsson T
Int Rev Cell Mol Biol 2019 ;346():157-200
Somatic mutation that affects transcription factor binding upstream of CD55 in the temporal cortex of a late-onset Alzheimer disease patient.
Helgadottir HT, Lundin P, Wallén Arzt E, Lindström AK, Graff C, Eriksson M
Hum Mol Genet 2019 08;28(16):2675-2685
Accumulation of Progerin Affects the Symmetry of Cell Division and Is Associated with Impaired Wnt Signaling and the Mislocalization of Nuclear Envelope Proteins.
Sola-Carvajal A, Revêchon G, Helgadottir HT, Whisenant D, Hagblom R, Döhla J, Katajisto P, Brodin D, Fagerström-Billai F, Viceconte N, Eriksson M.
J Invest Dermatol 2019 11;139(11):2272-2280.e12
Somatic mutagenesis in satellite cells associates with human skeletal muscle aging.
Franco I, Johansson A, Olsson K, Vrtačnik P, Lundin P, Helgadottir HT, Larsson M, Revêchon G, Bosia C, Pagnani A, Provero P, Gustafsson T, Fischer H, Eriksson M.
Nat Commun 2018 02;9(1):800
Emerging candidate treatment strategies for Hutchinson-Gilford progeria syndrome.
Strandgren C, Revêchon G, Sola-Carvajal A, Eriksson M.
Biochem Soc Trans 2017 12;45(6):1279-1293
Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time.
Revêchon G, Viceconte N, McKenna T, Sola Carvajal A, Vrtačnik P, Stenvinkel P, Lundgren T, Hultenby K, Franco I, Eriksson M.
Sci Rep 2017 06;7(1):4405
- European Joint program on Rare Diseases (EJPRD), coordinator 2020-2022
- European Society of Human Genetics
- American Society of Human Genetics
- 2018 Rönnberg's prize in aging and age-related diseases to Irene Franco
- 2019 Jeansson’s foundation to Irene Franco
- Torsten Söderbergs stiftelse
- European Joint Programme on rare Diseases
- National Bioinformatics Infrastructure Sweden Long-term Support
Looking for a BSc or MSc project?
Undergraduate students (BSc, MSc in Molecular biology or similar) with an interest in molecular genetics and who find our research of interest may send an email to Maria Eriksson. We usually accept one undergraduate student per semester. Please include a CV and a letter of interest.