8 Hematology in Older Persons Flashcards
Genetically determined syndromes with features of accelerated aging
Hutchison-Guilford (early-onset progeria), Werner (adult-onset progeria), and Down syndromes
Single gene mutation in Werner syndrome
chromosome 8
Encodes a protein containing a helicase-like domain
A mutation in the lamin A (LMNA) gene localized to chromosome 1 causes
Hutchison-Guilford syndrome
Hypothesis that a random or stochastic accumulation of damage, either to DNA or protein, that leads eventually to dysfunctional cells, cell death and subsequent organ dysfunction, and ultimately death.
Somatic mutation theory
Proposes that spontaneous or endogenous mutations occur at different rates in different species and that this accounts for the variability observed in lifespan
Intrinsic mutagenesis theory
Disorders involving one or a subset of repair mechanisms could lead to accumulation of DNA damage and dysfunction.
DNA repair theory
It is suggested that random errors in protein synthesis occur, and when the proteins involved are those responsible for DNA or RNA synthesis
Error catastrophe theory
Critical enzyme is necessary for maintaining telomere length and cell replicative potential
Telomerase
In vitro cellular senescence is associated with diminished telomerase activity but whether this relates to aging of the organism as a whole remains controversial.
This theory offers that aging is the result of DNA and protein damage (eg, mutagenesis or crosslinking) by atoms or molecules that contain unpaired electrons (free radicals).
Free radical hypothesis
Proposes that the decrements in neuronal and associated hormonal function are central to aging.
Neuroendocrine theory
After a finite number of divisions, normal somatic cells invariably enter a state of irreversibly arrested growth, a process termed _________________
Replicative senescence
The percentage of marrow space occupied by the hematopoietic tissue declines from _______at birth to a level of approximately _______at age 30 years and _______at age 70 years
90% at birth
50% at age 30 years
30% at age 70 years
The most apparent change seen in the marrow with aging is
Decreased cellularity
___________ (type of cell) numbers increase with age.
Monocyte
In humans, alterations occur in the phenotype and cell surface markers of monocytes: “nonclassical” CD14+CD16+ are increased compared with “classical” CD14+CD16- monocytes.
Nonclassical monocytes secrete proinflammatory cytokines but with unknown consequences.
By immunophenotyping of lymphoid and myeloid cell markers in humans, there are a preservation of numbers of myeloid cells and a decrease in B-lymphoid cells, resulting in _______________ predominance (lineage)
Myeloid predominance
