LTF
Lactotransferrin precursor (EC 3.4.21.-) (Lactoferrin) (Growth-inhibiting protein 12) (Talalactoferrin) [Contains: Lactoferricin-H (Lfcin-H); Kaliocin-1; Lactoferroxin-A; Lactoferroxin-B; Lactoferroxin-C] [GIG12] [LF]
Publications[править]
Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. The initial discovery analysis of 260 kidney transcriptomes from the TRANScriptome of renaL humAn TissuE Study (TRANSLATE) and the Cancer Genome Atlas identified 37 age-associated genes. For 19 of those genes, the association with age was replicated in 303 kidney transcriptomes from the Nephroseq resource. Surveying 42 nonrenal tissues from the Genotype-Tissue Expression project revealed that, for approximately a fifth of the replicated genes, the association with age was kidney-specific. Seventy-three percent of the replicated genes were associated with functional or histological parameters of age-related decline in kidney health, including glomerular filtration rate, glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arterial narrowing. Common genetic variants in four of the age-related genes, namely LYG1, PPP1R3C, LTF and TSPYL5, correlated with the trajectory of age-related changes in their renal expression. Integrative analysis of genomic, epigenomic, and transcriptomic information revealed that the observed age-related decline in renal TSPYL5 expression was determined both genetically and epigenetically. Thus, this study revealed robust molecular signatures of the aging kidney and new regulatory mechanisms of age-related change in the kidney transcriptome.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Computational Biology
- DNA Methylation
- Epigenomics
- Female
- Gene Expression Profiling
- Genetic Variation
- Glomerular Filtration Rate
- Humans
- Intracellular Signaling Peptides and Proteins
- Lactoferrin
- Male
- Middle Aged
- Muramidase
- Nephrons
- Nuclear Proteins
- RNA-Seq
- Renal Insufficiency, Chronic
- Transcriptome
Keywords
- aging
- epigenome
- genetics
- kidney
- transcriptome
The reason for increased sleep-disordered breathing with a predominance of central apneas in the elderly is unknown. We speculate that ventilatory control instability may provide a link between aging and the onset of unstable breathing during sleep. We sought to investigate potential underlying mechanisms in healthy, elderly adults during sleep. We hypothesized that there is 1) a decline in respiratory plasticity or long-term facilitation (LTF) of ventilation and/or 2) increased ventilatory chemosensitivity in older adults during non-, this should be hyphenated, non-rapid rapid eye movement (NREM) sleep. Fourteen elderly adults underwent 15, 1-min episodes of isocapnic hypoxia (EH), nadir O2 saturation: 87.0 ± 0.8%. Measurements were obtained during control, hypoxia, and up to 20 min of recovery following the EH protocol, respectively, for minute ventilation (VI), timing, and inspiratory upper-airway resistances (RUA). The results showed the following. 1) Compared with baseline, there was a significant increase in VI (158 ± 11%, P < 0.05) during EH, but this was not accompanied by augmentation of VI during the successive hypoxia trials nor in VI during the recovery period (94.4 ± 3.5%, P = not significant), indicating an absence of LTF. There was no change in inspiratory RUA during the trials. This is in contrast to our previous findings of respiratory plasticity in young adults during sleep. Sham studies did not show a change in any of the measured parameters. 2) We observed increased chemosensitivity with increased isocapnic hypoxic ventilatory response and hyperoxic suppression of VI in older vs. young adults during NREM sleep. Thus increased chemosensitivity, unconstrained by respiratory plasticity, may explain increased periodic breathing and central apneas in elderly adults during NREM sleep.
MeSH Terms
- Adult
- Aged
- Aging
- Chemoreceptor Cells
- Female
- Humans
- Long-Term Potentiation
- Male
- Middle Aged
- Polysomnography
- Pulmonary Ventilation
- Respiratory Mechanics
- Sleep Stages
- Young Adult
Keywords
- aging
- episodic hypoxia
- hypoxic ventilatory response
- intermittent hypoxia
- peripheral chemoreceptor activity
- ventilation