Age-related changes in human sublingual glands: a post mortem study

BackgroundAlternative mRNA transcripts occur in >90% of human genes and may be triggered by developmental signals. The hepatic transporter OATP1B1 (gene name SLCO1B1) traffics substrates across the hepatic membrane, and shows age-related changes in protein expression. We aimed to predict novel isoforms of OATP1B1 by studying alternative splicing of SLCO1B1 in human paediatric post-mortem liver tissue, and the relationship of their mRNA expression with age.Methods mRNA expression of SLCO1B1 transcripts was determined using RNA sequencing (HISAT2/StringTie). Novel mRNA transcripts were considered of relevance when (1) the expression was >5% of the annotated isoform, (2) it was a SLCO1B7 and SCLO1B1 hybrid transcript, or (3) when the expression was associated with age. The software packages ORF-finder, TMpred and TOPO2 were used to predict the protein sequence and structure of the novel isoforms. Relationship of expression with age was studied with the Kruskal-Wallis test for age groups (fetal, 0–1.5 year, 1.5–6 year, 6–12 year and 12–18 year) and with Spearman correlation tests for age on continuous scale.ResultsIn 97 hepatic post-mortem tissues (gestational age median 16.4 [range 14.7–41.3] weeks, postnatal age 0.36 [0 - 17] years) 27 novel mRNA transcripts were detected. Of these, 13 were relevant: 2 isoforms are predicted to translate into amino acid sequences similar to the annotated isoform for OATP1B1, 9 isoforms may translate into truncated versions, and the expression of 8 isoforms was associated with age. None of the isoforms had an ORF that covered the SLCO1B7 region.ConclusionWe showed that novel SLCO1B1 mRNA isoforms potentially translate into OATP1B1 protein with unknown function, and that alternative splicing may well be a regulatory mechanism for SLCO1B1 expression during development. This data provides a better understanding of age-related changes in the expression of OATP1B1, and, with that, potentially improves prediction of disposition of endogenous and exogenous substrates.Disclosure(s)BG was supported, in part, by the Ter Meulen fund 2018 provided by the Royal Dutch Academy of Sciences. The National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland is funded by the National Institutes of Health (NIH) contract HHSN275200900011C, reference number, N01-HD-9-0011 and the Liver Tissue Cell Distribution System is funded by NIH contract number N01-DK-7-0004/HHSN267200700004C.

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Age-related changes in the hyoid bone: An autopsy-based radiological analysis

Medicine Science and the Law ◽

10.1177/00258024211020278 ◽

2021 ◽

pp. 002580242110202

Author(s):

Devendra Jadav ◽

Rutwik Shedge ◽

Tanuj Kanchan ◽

Vikas Meshram ◽

Pawan Kumar Garg ◽

...

Keyword(s):

Age Estimation ◽

Hyoid Bone ◽

The Body ◽

Forensic Age Estimation ◽

Chronological Age ◽

Post Mortem ◽

Post Mortem Examination ◽

Bone Fusion ◽

Age Related ◽

Age Related Changes

Forensic age estimation is a crucial aspect of the biological profile of unidentified cadavers. The utility of age-related changes of hyoid bone fusion in forensic age estimation has not been explored much in the past. These age-related changes can be visualised in both the living and the dead using conventional radiography. These changes can assist medico-legal professionals and forensic anthropologists in the identification of unknown deceased, especially when the cadaver is mutilated or charred or when the other well-established indicators of skeletal and dental maturity are absent. The aims of this study were to evaluate age-related changes in the hyoid bone and to ascertain whether these changes may be utilised for age estimation in forensic examinations. The hyoid bone was carefully dissected using a standard procedure from 75 cadavers during post-mortem examination. The hyoid bone was radiographed, and the bone was replaced in the body cavity before the post-mortem examination was completed. Hyoid bone fusion was studied by using a standard grading method. Spearman’s correlation coefficient was calculated between the fusion scores and chronological age to assess their relationship. Box and whisker plots of fusion stage-wise age distribution were constructed to demonstrate the gradual linear relationship between hyoid bone fusion and the chronological age of the study participants. The present study concludes that hyoid bone fusion is an indicator of the chronological age of an individual and can be used in conjunction with other methods of age estimation such as the skeletal and dental age.

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Age-related changes in Tau and Autophagy in human brain in the absence of neurodegeneration

10.1101/2021.08.21.456385 ◽

2021 ◽

Author(s):

Amritpal Mudher ◽

Shreyasi Chatterjee ◽

Megan Sealey ◽

Eva Ruiz ◽

Chrysia Maria Pegasiou ◽

...

Keyword(s):

Therapeutic Potential ◽

Phosphorylated Tau ◽

Post Mortem ◽

Cognitively Normal ◽

Age Related ◽

Normal Individuals ◽

Drosophila Model ◽

Resected Tissue ◽

Age Related Changes

Tau becomes abnormally hyper-phosphorylated and aggregated in tauopathies like Alzheimers disease (AD). As age is the greatest risk factor for developing AD, it is important to understand how tau protein itself, and the pathways implicated in its turnover, change during aging. We investigated age-related changes in total and phosphorylated tau in brain samples from two cohorts of cognitively normal individuals spanning 19-74 years, without overt neurodegeneration. One cohort utilised resected tissue and the other used post-mortem tissue. Total soluble tau levels declined with age in both cohorts. Phosphorylated tau was undetectable in the post-mortem tissue but was clearly evident in the resected tissue and did not undergo significant age-related change. To ascertain if the decline in soluble tau was correlated with age-related changes in autophagy, three markers of autophagy were tested but only two appeared to increase with age and the third was unchanged. This implies that in individuals who do not develop neurodegeneration, there is an age-related reduction in soluble tau which could potentially be due to age-related changes in autophagy. Thus, to explore how an age-related increase in autophagy might influence tau-mediated dysfunctions in vivo, autophagy was enhanced in a Drosophila model and all age-related tau phenotypes were significantly ameliorated. These data shed light on age-related physiological changes in proteins implicated in AD and highlights the need to study pathways that may be responsible for these changes. It also demonstrates the therapeutic potential of interventions that upregulate turnover of aggregate-prone proteins during aging.

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Age-related changes in liver, gall bladder and pancreas

Reviews in Clinical Gerontology ◽

10.1017/s0959259802012133 ◽

2002 ◽

Vol 12 (1) ◽

pp. 12-20 ◽

Cited By ~ 2

Author(s):

Hilary A Wynne

Keyword(s):

Liver Volume ◽

Significant Negative Correlation ◽

Post Mortem ◽

Ultrasound Scanning ◽

Healthy Individuals ◽

Related Effect ◽

Liver Size ◽

Age Related ◽

Age Related Changes

Although a reduced liver size in elderly people has long been recognized from post-mortem studies, these studies do not allow the separation of true ‘age-related’ differences from the effects of premorbid illness, and death. An age-related effect was confirmed however by an in vivo study which measured liver size by ultrasound scanning of healthy individuals. This demonstrated a significant negative correlation between age and liver volume, with volumes being 28% lower in individuals above the age of 65 compared with those under 40 years of age.

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