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Unlike dietary restriction, rapamycin fails to extend lifespan and reduce transcription stress in progeroid DNA repair-deficient mice

Aging Cell - February 2021 Dietary restriction (DR) and rapamycin extend healthspan and life span across multiple species. We have recently shown that DR in progeroid DNA repair-deficient mice dramatically extended healthspan and trippled life span. Here, we show that rapamycin, while significantly lowering mTOR signaling, failed to improve life span nor healthspan of DNA repair-deficient Ercc1∆/- mice, contrary to DR tested in parallel. Rapamycin interventions focusing on dosage, gender, and timing all were [...]

Categorieën: Nieuws, Nieuws VOILA, Papers|

Emerging Role of C/EBPβ and Epigenetic DNA Methylation in Ageing

Trends in genetics - Volume 36, Issue 2, February 2020 Christof Niehrs (Institute of Molecular Biology), Cornelis F. Calkhoven (European Research Institute for the Biology of Ageing) Ageing is closely associated with and influenced by energy metabolism, and C/EBPβ is emerging as a key regulator of energy metabolism and longevity. DNA hypermethylation in GADD45α/ING1 mutant mice is associated with progeria due to a failure of TET-dioxygenase mediated demethylation of C/EBPβ binding sites. Accordingly, GADD45α/ING1 mutant [...]

Categorieën: Nieuws, Papers|

A meta-analysis of genome-wide association studies identifies multiple longevity genes

Nature Communications - Augustus 2019 Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous [...]

Categorieën: Nieuws, Papers|

Langlevendheid is vooral erfelijk in extreem langlevende families

Persbericht LUMC - 7 januari 2019 Een lang leven is erfelijk, maar dat geldt primair voor personen uit families waarvan meerdere leden behoren tot de top tien procent overlevers van hun generatie. In de genen van deze families ligt waarschijnlijk de sleutel tot een lang leven. Dat schrijven onderzoekers van het Leids Universitair Medisch Centrum samen met Amerikaanse en Nijmeegse collega’s in Nature Communications. De onderzoekers kwamen tot hun conclusies na het bestuderen van [...]

Categorieën: Nieuws, Papers, persberichten|

Eline Slagboom en collega’s publiceren Review in Nature over verouderingsonderzoek

Facing up to the global challenges of ageing Linda Partridge, Joris Deelen & P. Eline Slagboom Longer human lives have led to a global burden of late-life disease. However, some older people experience little ill health, a trait that should be extended to the general population. Interventions into lifestyle, including increased exercise and reduction in food intake and obesity, can help to maintain healthspan. Altered gut microbiota, removal of senescent cells, blood factors obtained from young individuals [...]

Categorieën: Nieuws, Papers|

Worms may hold the secret to longer life

Horizon - The EU Research & Innovation Magazine 5 juli 2018 The regenerative abilities of the flatworm Macrostomum lignano serve as a model for how humans might regenerate tissues. Image credit - Flickr/ Lukas Schärer, licensed under CC BY-SA 2.0 Research into the remarkable regenerative powers of worms and the insights they can give into battling diseases could help humans live longer and healthier lives. Humans have long dreamed of finding the secret to [...]

Categorieën: Nieuws, Papers|

Reduced expression of C/EBPβ-LIP extends health and lifespan in mice

E life Sciences| 30 april 2018 Abstract Ageing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBPβ-LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame [...]

Categorieën: Nieuws, Papers|

DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood

Science Advances | 03-01-2018 Abstract Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide [...]

Categorieën: Nieuws, Papers|

A p300 and SIRT1 Regulated Acetylation Switch of C/EBPa Controls Mitochondrial Function

Cell Press  | 9 januari 2018 | Summary Cellular metabolism is a tightly controlled process in which the cell adapts fluxes through metabolic  pathways in response to changes in nutrient supply. Among the transcription factors that regulate  gene expression and thereby cause changes in cellular metabolism is the basic leucine-zipper (bZIP) transcription factor CCAAT/enhancer-binding protein alpha (C/EBPa). Protein lysine acetylation is a key post-translational modification (PTM) that integrates cellular metabolic cues with other  physiological [...]

Categorieën: Nieuws, Papers|

Plasticity of lifelong calorie-restricted C57BL/6J mice in adapting to a medium-fat diet intervention at old age

Aging Cell | 23-09-2017| Summary Calorie restriction (CR) is a dietary regimen that supports healthy aging. In this study, we investigated the systemic and liver-specific responses caused by a diet switch to a medium-fat (MF) diet in 24-month-old lifelong, CR-exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine-week-old C57BL/6J mice were exposed either to a control, CR, or MF diet. At the age of 24 [...]

Categorieën: Papers|
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