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Nuclear insertions of mitochondrial DNA (mtDNA) segments (NUMTs) represent an evolutionarily conserved phenomenon originating from the ancient endosymbiotic relationship between mitochondria and host cells. These insertions predominantly localize near intergenic or regulatory regions and are often enriched in tissues with high metabolic activity. Once regarded as inert pseudogenes or genomic artifacts, NUMTs are now recognized as dynamic elements capable of modulating nuclear architecture and...

Calcium (Ca^(2+))/calmodulin (CaM)-dependent protein kinase II (CaMKII) is an emerging drug target for age-related diseases. It is a multifunctional kinase with complex activation modes, numerous isoforms, broad tissue distribution, and a dual role in health and disease. In particular, its isoforms share a high degree of conservation within the catalytic and regulatory domains, with only minor differences confined to the linker region. These characteristics of CaMKII make the development of...

Wiedemann-Rautenstrauch syndrome (WRS) is a rare neonatal progeroid disorder primarily associated with pathogenic variants in POLR3A. However, the pathogenicity of certain variants remains unclear. Here, we report a WRS case carrying the POLR3A c.2707G > A (p.Gly903Arg) variant and explore its potential role in disease pathogenesis through in silico predictive and structural modeling analyses. Evolutionary conservation analysis, along with functional impact predictions from Provean, SIFT,...

CONCLUSIONS AND IMPLICATIONS: We identify LOS predictors to aid in discharge planning and introduce the "healthy elder effect" hypothesis into literature.

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Aging is the main risk factor for Parkinson's disease (PD), yet our understanding of how age-related mechanisms contribute to PD pathophysiology remains limited. We conducted a longitudinal analysis of blood samples from the Parkinson's Progression Markers Initiative cohort to investigate DNA damage in PD. Patients with PD exhibited disrupted DNA repair pathways and biased suppression of longer transcripts, indicating age-related, transcription-stalling DNA damage. Notably, at the intake visit,...

Hematopoietic multipotent progenitors (MPPs) regulate blood cell production to meet the evolving demands of an organism. Adult human MPPs remain ill defined, whereas mouse MPPs are well characterized, with distinct immunophenotypes and lineage potencies. Using multi-omic single-cell analyses and functional assays, we identified distinct human MPPs within Lin-CD34+CD38dim/lo adult bone marrow with unique biomolecular and functional properties. These populations were prospectively isolated based...

Age-related deterioration in bone strength among Western humans has been linked with sedentary lifestyles, but the effect remains debatable. We evaluated aging of diaphyseal strength and cortical bone loss in a European Holocene sample of 1881 adult humeri, femora, and tibiae. Diaphyseal aging did not differ between Early and Late Holocene adults, despite their differences in physical activity. Adult diaphyseal aging was accompanied by the disproportionate rate between a faster increase in the...

Aging, and by extension age-related diseases, has traditionally been understood through classical evolutionary genetic models, such as the mutation accumulation and antagonistic pleiotropy theories. However, these frameworks primarily focus on the declining efficacy of organismal-level selection against mutations with deleterious effects in late life. Here, we propose a novel hypothesis: many chronic diseases associated with aging may emerge, at least in part, as a result of selection acting at...

INTRODUCTION: Cancer is associated with accelerated aging, including changes in muscle composition and cognition. However, the relationship between myosteatosis and cognitive function has not been investigated in older cancer survivors. This study evaluated the association between myosteatosis and cognitive function in this population.

Mitochondrial sirtuins regulate metabolism and are emerging drug targets for metabolic and age-related diseases such as cancer, diabetes, and neurodegeneration. Yet, the extent of their functions remain unclear. Here, we uncover a physiological role for the C. elegans mitochondrial sirtuins, sir-2.2 and sir-2.3, in lifespan regulation. Using genetic alleles with deletions that destroy catalytic activity, we demonstrate that sir-2.2 and sir-2.3 mutants live an average of 25% longer than controls...

CONCLUSION: Our findings underscore the importance of individual-level analyses in aging research. While QoL may appear stable at the group level, individual trajectories vary considerably. This has important implications for the use of QoL as a primary endpoint in clinical trials, particularly in geriatric populations. Notably, age alone did not significantly influence QoL over time.

Age-related hearing loss (ARHL), or presbycusis, is characterized by a progressive decline in binaural auditory sensitivity, particularly affecting high-frequency hearing and sound localization. The pathogenesis of ARHL is still unclear, correspondingly reflected in a lack of clinically effective intervention strategies. Recent advancements in audiology and neurobiology have illuminated the black box of the pathogenesis of ARHL. The intricate mechanisms underlying ARHL involve inflammation,...

Abandoning long-standing vaccine requirements for schoolchildren could prompt bigger outbreaks, researchers warn