Age-related change in human haematopoiesis causes reduced regenerative capacity, cytopenias, immune dysfunction and increased risk of blood cancer, but the reason for such abrupt functional decline after 70 years of age remains unclear. Here we sequenced 3,579 genomes from single cell-derived colonies of haematopoietic cells across 10 human subjects from 0 to 81 years of age. Haematopoietic stem cells or multipotent progenitors (HSC/MPPs) accumulated a mean of 17 mutations per year after birth and lost 30 base pairs per year of telomere length. Haematopoiesis in adults less than 65 years of age was massively polyclonal, with high clonal diversity and a stable population of 20,000-200,000 HSC/MPPs contributing evenly to blood production. By contrast, haematopoiesis in individuals aged over 75 showed profoundly decreased clonal diversity. In each of the older subjects, 30-60% of haematopoiesis was accounted for by 12-18 independent clones, each contributing 1-34% of blood production. Most clones had begun their expansion before the subject was 40 years old, but only 22% had known driver mutations. Genome-wide selection analysis estimated that between 1 in 34 and 1 in 12 non-synonymous mutations were drivers, accruing at constant rates throughout life, affecting more genes than identified in blood cancers. Loss of the Y chromosome conferred selective benefits in males. Simulations of haematopoiesis, with constant stem cell population size and constant acquisition of driver mutations conferring moderate fitness benefits, entirely explained the abrupt change in clonal structure in the elderly. Rapidly decreasing clonal diversity is a universal feature of haematopoiesis in aged humans, underpinned by pervasive positive selection acting on many more genes than currently identified.
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http://dx.doi.org/10.1038/s41586-022-04786-y | DOI Listing |
BMC Public Health
December 2024
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-Sen University, Guangzhou, 510060, China.
Background: Retinal microvascular abnormalities (RMA) reflect cumulative microvascular damage from systemic diseases and aging. However, little is known about the association between RMA and long-term survival outcomes. This study aimed to examine the relationships between RMA and the risk of all-cause and specific-cause mortality among U.
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December 2024
Pediatric Surgery Dept, Al-Azhar university, Cairo, Egypt.
Background: Complications after male circumcision are numerous and may be presented as an adhesion between the glans penis and the preputial remnants, these adhesions may acquire different forms and troublesome the affected children.
Patients And Methods: This is a retrospective study of 95 consecutive children of presumed glanular-preputial adhesions referred for correction of circumcision. They were assessed and classified as having either an early preputial adhesion or a well-formed skin bridge into 2 groups; group (A) who have a simple adhesion that was resolved through a conservative preputial adhesiolysis while those in the group (B) had a well-formed skin bridge, which deserves surgical correction.
BMC Public Health
December 2024
Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Türkiye.
Objectives: This cross-sectional study aimed to explore the frequency of breast refusal (BR), associated factors including postpartum depression and breastfeeding self-efficacy, and investigate the recovery status following BR.
Methods: The survey comprised four sections, to investigate the sociodemographic characteristics of mothers and their babies, Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF), the Edinburgh Postnatal Depression Scale (EPDS) of mothers, and features associated with BR. The survey was administered online to those with babies aged 0-24 months.
BMC Musculoskelet Disord
December 2024
Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
Background: Achondroplasia, the most common form of rhizomelic dwarfism, occurs in approximately 1 in 25,000 individuals. Clinical features include attenuated growth, rhizomelic limb shortening, and craniofacial abnormalities. Limb-lengthening surgery is widely employed to improve quality of life.
View Article and Find Full Text PDFBMC Geriatr
December 2024
Université de Paris, EA 4468, APHP, Hôpital Broca, Paris, France.
Background: Older age and associated comorbid conditions increase the risk of severe form of COVID-19 and death. The SARS-CoV-2 vaccination campaign began in France in December 2020 targeting institutionalized older population before having been evaluated in this population. The objective of our study was to assess the tolerability of vaccination 21 days (D21) and 90 days after the first vaccination (D90) in institutionalized old people.
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