Nano-Vesicle (Mis)Communication in Senescence-Related Pathologies

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role in cell-cell communications. Exosomes have evolved as potential biomarkers for aging-related diseases. Aging, a physiological process, involves a progressive decline of function of organs with a loss of homeostasis and increasing probability of illness and death. The review focuses on the classic view of exosome biogenesis, biology, and age-associated changes. Owing to their ability to transport biological information among cells, the review also discusses the interplay of senescent cell-derived exosomes with the aging process, including the susceptibility of the aging population to COVID-19 infections

Histone deacetylases 1 and 2 silence cryptic transcription to promote mitochondrial function during cardiogenesis

Cryptic transcription occurs widely across the eukaryotic genome; however, its regulation during vertebrate development is not understood. Here, we show that two class I histone deacetylases, Hdac1 and Hdac2, silence cryptic transcription to promote mitochondrial function in developing murine hearts. Mice lacking Hdac1 and Hdac2 in heart exhibit defective developmental switch from anaerobic to mitochondrial oxidative phosphorylation (OXPHOS), severe defects in mitochondrial mass, mitochondrial function, and complete embryonic lethality. Hdac1/Hdac2 promotes the transition to OXPHOS by enforcing transcriptional fidelity of metabolic gene programs. Mechanistically, Hdac1/Hdac2 deacetylates histone residues including H3K23, H3K14, and H4K16 to suppress cryptic transcriptional initiation within the coding regions of actively transcribed metabolic genes. Thus, Hdac1/2-mediated epigenetic silencing of cryptic transcription is essential for mitochondrial function during early vertebrate development

Multifaceted role of cardiovascular biomarkers

Cardiovascular diseases, a global health issue, claim the lives of many every year. Lifestyle changes and genetic predisposition are the key drivers for the development of CVDs. In many of the patients, the disease is detected at the end stage making heart transplantation the only treatment option. Hence every attempt should be made to identify the risk at an early stage and initiate preventive measures to improve the quality of their life. Biomarkers are one of the critical factors that aid in the early diagnosis of CVDs. More specific and highly sensitive biomarkers have been discovered lately and have been employed for prognosis and diagnosis of CVDs. The present review briefs about the various categories of cardiovascular biomarkers with emphasis on novel biomarkers and discusses the biomarkers employed for different purposes in CVDs. The biomarkers have also helped in identifying COVID-19 patients with increased risk for developing cardiovascular complications. Being non-invasive makes biomarkers advantageous over other methods for evaluating the pathophysiological status of CVDs

Age associated variation in migration efficiency of CSCs from WST and SHR.

<p><b>(a)</b> Representative photograph of migrated CSCs as observed by trans-well assay. <b>(b)</b> Graphical representation of migration ability represented as mean number of cells/field (n = 3) Data presented as mean ± SD. Variation was analysed by two way ANOVA followed by Student t-test. (** p<0.01 SHR Vs Age matched WST; †† p<0.01 and † p<0.05 WST & SHR of different ages compared to respective 1 week old pups. Two way ANOVA p<0.001).</p

Accelerated decline in cardiac stem cell efficiency in Spontaneously hypertensive rat compared to normotensive Wistar rat - Fig 5

<p><b>Age associated variation in cardiovascular differentiation of CSCs from WST and SHR determined by Western blot analysis</b> Representative blots and graphical representation of the expression of <b>(a)</b> Cardiac troponin I and <b>(b)</b> smooth muscle actin (n = 3) Data presented as mean ± SD. Variation was analysed by two way ANOVA followed by Student t-test. (†† p<0.01 and † p<0.05 WST & SHR of different ages compared to respective 1 week old pups. Two way ANOVA p<0.001).</p

Age associated variation in the proportion of senescent CSCs in WST and SHR.

<p><b>(a)</b> Graphical representation of percentage of senescent cells (n = 3) <b>(b)</b> Representative blots and graphical representation of p16^ink4a protein expression (n = 3) <b>(c)</b> Representative blots and graphical representation of p21 protein expression (n = 3) Data presented as mean ± SD. Variation was analysed by two way ANOVA followed by Student t-test. **p<0.01 SHR Vs Age matched WST; †† p<0.01 and WST & SHR of different ages compared to respective 1 week old pups. Two way ANOVA p<0.001).</p

Age associated variation in ROS levels of CSCs of WST and SHR based on H2DCFDA fluorescence.

<p>Data presented as mean ± SD. (n = 3) Variation was analysed by two-way ANOVA followed by Student t-test. (**p<0.01 and * p<0.05 SHR Vs age matched WST; and †† p<0.01 WST & SHR of different ages compared to respective 1 week old pups. Two way ANOVA p<0.001).</p

Sequence of Oligionucleotide primers.

<p>Sequence of Oligionucleotide primers.</p

Age associated variation in the proportion of c-kit⁺ CSCs in ventricular digests from SHR and Wistar rats.

<p>Graphical representation of data expressed as percentage of total cells. (n = 3). Data presented as mean ± SD. Variation was analysed by two way ANOVA followed by Student t-test. (** p<0.01 and * p<0.05 SHR Vs Age matched WST; †† p<0.01 and † p<0.05 WST & SHR of different ages compared to respective 1 week old pups. Two way ANOVA p<0.001).</p

Age associated variation in expression of TERT mRNA, telomerase activity and level of DNA damage in SHR and Wistar rat.

<p><b>(a)</b> Graphical representation of TERT mRNA levels expressed as fold change (n = 3) <b>(b)</b> Representative photograph of telomerase activity <b>(c)</b> Graphical representation of telomerase activity (n = 3) <b>(d)</b> Representative photograph of DNA damage as evaluated by Comet assay <b>(e)</b> Graphical representation of DNA damage represented as comet tail moment (n = 3) Data presented as mean ± SD. Variation was analysed by two way ANOVA followed by Student t-test. **p<0.01 SHR Vs age matched WST; †† p<0.01 and † p<0.05 WST & SHR of different ages compared to respective 1 week old pups. Two way ANOVA p<0.001).</p