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A blood-based DNA damage signature in patients with Parkinson's disease is associated with disease progression

1 month 3 weeks ago
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,...
Daisy Sproviero

A single-cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis

1 month 3 weeks ago
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...
Asiri Ediriwickrema

Bone health: Age-related changes in diaphyseal structural properties among European Holocene humans during the last 9000 years

1 month 3 weeks ago
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...
Vladimír Sládek

The Role of Selection for Function in Aging and Chronic Diseases: A Novel Evolutionary Perspective

1 month 3 weeks ago
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...
Antoine M Dujon

Mitochondrial sirtuins sir-2.2 and sir-2.3 regulate lifespan in C. elegans

1 month 3 weeks ago
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...
Sarah M Chang

Age-related trajectories of quality of life in community dwelling older adults: findings from the Survey of Health, Aging and Retirement in Europe (SHARE)

1 month 3 weeks ago
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.
Sarah Mendorf

Pathophysiological insights and therapeutic developments in age-related hearing loss: a narrative review

1 month 3 weeks ago
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,...
Shichu Sun