Åldrande – molekylära mekanismer och interventioner – Christian Riedels forskargrupp

Åldrande och åldersrelaterade sjukdomar är centrala begrepp för människors hälsa. Vår forskning rör åldrandets molekylära mekanismer och hur processer relaterade till åldrande kan motverkas.

En del av:

Vår forskning

Även om vår hälsa och livslängd styrs av hur snabbt vi åldras så är denna hastighet inte förutbestämd utan kan påverkas. I vår forskargrupp använder vi rundmasken Caenorhabditis elegans som modellsystem för att förstå de mekanismer som kan skynda på eller sakta ner åldrandeprocessen. C. elegans är en idealisk modellorganism för forskning kring åldrande tack vare sina väletablerade metoder och verktyg, korta livslängd och höga känslighet för moduleringar av processer som styr åldrande. Vi studerar även motsvarande processer i mänskliga celler för att göra det möjligt att använda våra resultat i terapeutiskt syfte. Slutligen utvecklar och tillämpar vi screeningstrategier för att identifiera ämnen som kan motverka åldrande och som har hög sannolikhet att fungera på människor.

I vår forskning kombinerar vi biokemi (proteomik, ChIP-Seq, mRNA-Seq, ATAC-Seq,…) med storskaliga bioinformatiska, genetiska och farmakologiska screeningstrategier för att förstå hur åldrande regleras på molekylär och mekanistisk nivå och för att identifiera sätt att motverka dessa processer.

Mer information om gruppen finns på den engelska sidan. 

Publikationer

Utvalda publikationer

Finansiering

Forskningsbidrag

  • Swedish Research Council
    1 January 2024 - 31 December 2027
    Aging is the biggest risk factor for human morbidity and mortality, caused by damage accumulation and resulting functional decline of the organism over time. Fortunately, aging can be interfered with, and thus detailed mechanistic understanding of the underlying pathways could instruct powerful therapies to extend our healthspan and lifespan. Our research focuses on one of the most powerful aging regulators, the insulin/IGF signaling (IIS) pathway, relaying nutrient scarcity into a transcriptional program that improves stress resistance, slows damage accumulation, and ultimately defers aging. Much of this program is driven by the transcription factor (TF) DAF-16/FOXO, but it has long been thought that also the chromatin landscape could play an important role in its coordination. Indeed, by ATAC-seq we identified vast changes in chromatin accessibility under reduced IIS, and through different approaches we identified four chromatin-associated proteins that either confer or utilize these changes to contribute to the aging-preventive transcriptional outcomes. These include two chromatin-associated proteins that directly bind to DAF-16/FOXO, namely BAF-1 and PQN-51, and two TFs that bind enhancer regions which open up under reduced IIS, LIN-39 and LIN-32. Each of them are essential for reduced IIS to prevent aging but they function through distinct mechanisms of action, and we think that their full understanding will provide exciting new insights into aging prevention.
  • Swedish Cancer Society
    1 January 2024
    Despite many years of intensive research, there is currently a lack of effective treatment options for many types of cancer. It is clear that to be able to cure more forms of cancer, new therapeutic strategies are required. Treatment of cancer is today focused on the cancer cells themselves, but it is now clear that cancer requires interaction between the cancer cells and surrounding cells, which are in themselves healthy but which support the cancer cells. The molecular mechanisms that make up the interaction between cancer cells and surrounding tissue are currently incompletely mapped. A characteristic of most cancer cells is that they carry an abnormal number of chromosomes compared to normal cells, a condition known as aneuploidy. This chromosomal imbalance facilitates the cancer cells' ability to usurp extreme properties, such as uncontrolled growth through cell division. However, aneuploidy also involves a strain on basal cellular mechanisms. New data indicate that such cellular stress leads to the secretion of signaling molecules that can affect surrounding normal cells. In this project, we wish to validate the existence of this communication between cells and investigate whether it is important in tumor diseases. To begin with, we hope to confirm the existence of this new form of communication between cancer cells and their cellular neighbors in the local tissue. If this works, we will map the underlying molecular mechanisms and test whether they are required for cancer cell survival and the ability to form tumors. If so, manipulation of these communication mechanisms may represent a new strategy for treating cancer.
  • A new mechanism by which mitochondria modulate the outcomes of reduced insulin/IGF-like signaling and slow down the aging process
    Novo Nordisk Foundation
    1 January 2023 - 31 December 2024
  • Swedish Research Council
    1 January 2022 - 31 December 2024
  • A new mechanism by which mitochondria modulate the outcomes of reduced insulin/IGF-like signaling and slow down the aging process
    Novo Nordisk Foundation
    1 January 2022 - 31 December 2022
  • National Institute on Aging
    15 August 2021 - 31 July 2026
    PROJECT SUMMARY Age is the major risk factor for Alzheimer´s disease (AD), and as the world’s population is becoming older it is increasingly prevalent. There are many commonalities between aging and AD, both on the molecular and systems level. There is also ample evidence, in particular from work in animal models, that a broad spectrum of aging-preventive interventions that confer longevity have the ability to alleviate diverse aspects of AD pathology, such as Aβ and tau aggregation. These pathologies lead to severe neurodegeneration and occurrence of clinical symptoms such as memory loss, mood swings and changes in personality. No disease-modifying treatments exist, only medications that relieve the symptoms temporarily. To find treatments that prevent disease progression, testing drugs that have already been approved for other indications – a strategy referred to as drug repurposing – may be useful. A major benefit of drug repurposing is that it speeds up drug development and reduces the risks for patients, since these drugs have already passed safety assessment in humans. Thus, we propose a data-driven approach to search among drugs used for other age-related conditions and identify some that can be repurposed for the prevention of AD. Towards this approach, we will investigate the effect of the 20 most commonly used drug classes among 65+ year-olds in Sweden (>200 substances also approved for use in the U.S.) on biological aging and AD in a series of epidemiological analyses. We will use deeply phenotyped longitudinal cohort data to see how drug treatment changes biological aging trajectories, as well as apply Mendelian Randomizations to mimic the modulation on drug targets using large-scale genotyping data and emulated target trials in the Swedish Prescribed Drug Register linked to a quality register on dementia. Following this, the individual substances within the 2-3 most promising drug classes will be screened in vitro in human cellular models of AD and in vivo in C. elegans models of aging and of human Aβ and tau aggregation and toxicity. Top candidates will be tested in established and most relevant AD mouse models and in models of accelerated aging. Taken together, our approach to discover new drugs for AD prevention by screening already approved substances bears great benefits. The fact that much of the testing happens in silico and that the screening focuses only on drugs that are already approved for use in patients makes our approach faster and more cost- effective than conventional de novo compound screens.
  • Swedish Cancer Society
    1 January 2021
    Despite many years of intensive research, there is currently a lack of effective treatment options for many types of cancer. It is clear that to be able to cure more forms of cancer, new therapeutic strategies are required. Treatment of cancer is today focused on the cancer cells themselves, but it is now clear that cancer requires interaction between the cancer cells and surrounding cells, which are in themselves healthy but which support the cancer cells. The molecular mechanisms that make up the interaction between cancer cells and surrounding tissue are currently incompletely mapped. A characteristic of most cancer cells is that they carry an abnormal number of chromosomes compared to normal cells, a condition known as aneuploidy. This chromosomal imbalance facilitates the cancer cells' ability to usurp extreme properties, such as uncontrolled growth through cell division. However, aneuploidy also involves a strain on basal cellular mechanisms. New data indicate that such cellular stress leads to the secretion of signaling molecules that can affect surrounding normal cells. In this project, we wish to validate the existence of this communication between cells and investigate whether it is important in tumor diseases. To begin with, we hope to confirm the existence of this new form of communication between cancer cells and their cellular neighbors in the local tissue. If this works, we will map the underlying molecular mechanisms and test whether they are required for cancer cell survival and the ability to form tumors. If so, manipulation of these communication mechanisms may represent a new strategy for treating cancer.
  • Swedish Research Council
    1 January 2020 - 31 December 2023
  • Swedish Research Council
    1 December 2017 - 31 December 2022
  • Swedish Research Council
    1 January 2016 - 31 December 2019
  • Molecular mechanisms of longevity control
    International Human Frontier Science Program Organization
    1 May 2008 - 30 April 2011
Nyckelord:
Cell- och molekylärbiologi Genetik och genomik (Medicinska aspekter under 30107 och lantbruksvetenskapliga under 40402) Medicinsk bioinformatik och systembiologi Medicinsk genetik och genomik Åldrande
Innehållsgranskare:
Christian Riedel
Karin Vikström
2025-10-06