GeroScience, Год журнала: 2024, Номер unknown
Опубликована: Авг. 8, 2024
Язык: Английский
Cell Metabolism, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Science Advances, Год журнала: 2025, Номер 11(15)
Опубликована: Апрель 11, 2025
Telomere length regulation is essential for genome stability as short telomeres can trigger cellular senescence and apoptosis constituting an integral aspect of biological aging. biology disorders (TBDs) such dyskeratosis congenita (DC) are rare, inherited diseases with known mutations in at least 16 different genes encoding components the telomere maintenance complexes. The precise role TEN1, part CST complex (CTC1, STN1, TEN1), consequences its loss function vivo not yet known. We investigated first viable murine model Ten1 deficiency created by CRISPR-Cas9–mediated exon 3 deletion. homozygous knockout mice present attrition, life span, skin hyperpigmentation, aplastic anemia, cerebellar hypoplasia. Molecular analyses revealed a reduction proliferating cells, increased apoptosis, stem cell depletion activation p53/p21 signaling pathway. Our data demonstrate that causes shortening associates accelerated
Язык: Английский
Процитировано
0
Science Advances, Год журнала: 2025, Номер 11(16)
Опубликована: Апрель 16, 2025
Aging is associated with dysregulated methionine metabolism and increased levels of enzymes in the tyrosine degradation pathway (TDP). To investigate efficacy targeting either or TDP for healthspan improvement advanced age, we initiated dietary MetR inhibition 18-month-old C57BL/6J mice. significantly improved neuromuscular function, metabolic health, lung frailty. In addition, confirmed function from 5XFAD mice, whose weight was not affected by MetR. We did observe benefits inhibition. Single-nucleus RNA ATAC sequencing muscle revealed cell type–specific responses to MetR, although affect mouse aging epigenetic clock markers. Similarly, an 8-week intervention a human trial (NCT04701346) showed no significant impact on clocks. The observed late-life provide translational rationale develop mimetics as antiaging intervention.
Язык: Английский
Процитировано
0
Ageing Research Reviews, Год журнала: 2024, Номер 97, С. 102295 - 102295
Опубликована: Апрель 6, 2024
Язык: Английский
Процитировано
2
The Journals of Gerontology Series A, Год журнала: 2024, Номер 79(9)
Опубликована: Авг. 10, 2024
For centuries, aging was considered inevitable and immutable. Geroscience provides the conceptual framework to shift this focus toward a new view that regards as an active biological process, age of individual modifiable entity. Significant steps forward have been made identification biomarkers for measures age, yet knowledge gaps in geroscience are still numerous. Animal models perspective, which discusses how experimental design can be optimized inform refine development translationally relevant age. We provide recommendations field, including: longitudinal studies subjects deeply phenotyped via repeated multilevel behavioral/social/molecular assays; need consider sociobehavioral variables species studied; finally, importance assessing onset, severity pathologies, age-at-death. highlight approaches integrate functional impairment using machine learning designed estimate well predict future health declines mortality. expect advances animal will crucial translational but also next chapter medicine.
Язык: Английский
Процитировано
2
Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 29, 2024
Язык: Английский
Процитировано
2
GeroScience, Год журнала: 2024, Номер unknown
Опубликована: Авг. 8, 2024
Язык: Английский
Процитировано
0