The immune synapses reveal aberrant functions of CD8 T cells during chronic HIV infection

It is well-established that chronic HIV infection causes persistent low-grade inflammation that induces premature aging of the immune system in HIV patient including senescence of memory and effector CD8 T cells. To uncover the reasons of gradually diminished potency of CD8 T cells from chronically HIV infected people, we have analyzed cellular morphology and dynamics of the synaptic interface followed exposure of peripheral polyclonal CD8 T cells at various differentiation stages to planar lipid bilayers. The above parameters were linked to pattern of degranulation that determines efficiency of CD8 T cells cytolytic response. We found a large fraction of naive T cells from HIV infected people developing mature synapses and demonstrating focused degranulation, a signature of a differentiated T cells. Further differentiation of aberrant naive T cells leads to development of anomalous effector T cells undermining their capacity to control HIV and other viruses that could be contained otherwise.

Telomere elongation in the gut extends zebrafish lifespan

Telomere shortening is a hallmark of aging and is counteracted by telomerase. The gut is one of the earliest organs to exhibit short telomeres and tissue dysfunction during normal zebrafish aging. This is recapitulated in prematurely aged telomerase mutants (tert-/-). Here, we show that gut-specific telomerase activity in tert-/- zebrafish prevents premature aging. Induction of telomerase rescues gut senescence and low cell proliferation to wild-type levels, while restoring gut tissue integrity, inflammation, and age-dependent gut microbiota dysbiosis. Remarkably, averting gut dysfunction results in a systemic beneficial impact. Gut-specific telomerase activity rescues premature aging markers in remote organs, such as the reproductive (testes) and hematopoietic (kidney marrow) systems. Functionally, it also rescues age-dependent loss of male fertility and testes atrophy. Finally, we show that gut-specific telomerase activity increases the lifespan of telomerase mutants. Our work demonstrates that delaying telomere shortening in the gut is sufficient to systemically counteract aging in zebrafish.

Inherited human Apollo deficiency causes severe bone marrow failure and developmental defects

Inherited bone marrow failure syndromes (IBMFS) represent a group of disorders typified by impaired production of one or several blood cell types. The telomere biology disorders dyskeratosis congenita (DC) and its severe variant Høyeraal-Hreidarsson (HH) syndrome are rare IBMFS characterized by bone marrow failure, developmental defects, and various premature aging complications associated with critically short telomeres. Here we identified biallelic variants in the gene encoding the 5'-to-3' DNA exonuclease Apollo/SNM1B in three unrelated patients presenting with a DC/HH phenotype consisting of early onset hypocellular bone marrow failure, B and NK lymphopenia, developmental anomalies, microcephaly and/or intrauterine growth retardation. All three patients carry a homozygous or compound heterozygous (in combination with a null-allele) missense variant affecting the same residue L142 (L142F or L142S) located in the catalytic domain of Apollo. Apollo-deficient cells from patients exhibited spontaneous chromosome instability and impaired DNA repair that was complemented by CRISPR/Cas9-mediated gene correction. Furthermore, patients' cells showed signs of telomere fragility that were however not associated with global reduction of telomere length. Unlike patients' cells, human Apollo KO HT1080-cell lines showed strong telomere dysfunction accompanied by excessive telomere shortening, suggesting that the L142S and L142F Apollo variants are hypomorphic. Collectively, these findings define human Apollo as a genome caretaker and identify biallelic Apollo variants as a genetic cause of a hitherto unrecognized severe IBMFS combining clinical hallmarks of DC/HH with normal telomere length.

The Utilization of Wuluh Starfruit for Making Facial Cleansing Solid Soap

Belimbing wuluh is one of the species in the family (Averrhoa). It is estimated that this plant comes from tropical America, this plant grows well in its country of origin, while Indonesia is mostly kept in the yard and sometimes grows wild in the fields or forest edges. In general, wuluh starfruit for the people of Aceh is used as a spice called sunti acid. Starfruit can also be used as a raw material for making soap which has properties to inhibit premature aging and overcome acne problems because starfruit contains vitamins A and C.Belimbing wuluh is also known as a plant that grows in the yards of Acehnese houses, which every time it bears fruit it will produce quite a lot of fruit, if it is not used for making processed products, the fruit will rot on the tree or fall on the ground. Based on the abundant raw materials, this research will focus on "Utilization of Starfruit for Making Facial Cleansing Solid Soap". The purpose of this research is to make solid soap with additional ingredients of starfruit, and produce solid facial soap from starfruit in the form of face wash sticks so that it is easy to use. The research method used is an experimental method which produces three samples that meet the 2016 SNI standard with a moisture content of 10% and a degree of acidity (pH) 10. From the three samples, the first sample had a hardness that matches the characteristics of solid soap.

Horticultural Study on Cucumber Cultivation; Pest and Disease Control from Traditional Approach

The aims of the study to know Horticultural Study on Cucumber Cultivation; Pest and Disease Control from Traditional Approach. Cucumber offers several health advantages, including a high concentration of Vitamin A, anti-cancer properties, the ability to absorb pollutants, and the ability to provide energy. cucumber is high in provitamin A, which helps to preserve eye health by acting as an antioxidant. It also helps to prevent damage to body cells that leads to premature aging by acting naturally. cucumber fruit has been shown to be effective in reducing the development of intestinal cancer.

Modern Approaches to Diagnostics and Correction of Aging Biomarkers

From the biomedicine point of, view ageing is a natural process, characterized by a gradual decrease in the physiological integrity and adaptive abilities of the body, leading to a violation of its functions and an increase in the risk of death with age. Demographic aging of the population is a serious socio-economic problem, both in Russia and around the world. The main cellular and molecular signs of aging include genome instability, telomere shortening, epigenetic alterations, impaired proteostasis, impaired nutrient recognition, mitochondrial dysfunction, cellular aging, the stem cell pool depletion and changes in intercellular interaction, extracellular matrix rigidity, as well as activation of retrotransposons and chronic inflammation. For these reasons, in modern healthcare, preventing premature aging and treating age-related diseases is becoming a priority task. This review presents modern approaches to the quantitative assessment of the aging process using aging biomarkers as functional parameters reflecting the biological organism age at the molecular, cellular, and organismal levels. This work also considers the actual non-drug and drug interventions allowing to slow down the development of age-associated pathological processes, allowing you to increase the quality and duration of life.

Plasma EFEMP1 Is Associated with Brain Aging and Dementia: The Framingham Heart Study

Background: Epidermal growth factor containing fibulin extracellular matrix protein-1 (EFEMP1) has been associated with increased white matter hyperintensities (WMH) burden and disorders of premature aging and may have a shared pathophysiological role in the development of WMH and dementia. Objective: To determine the association between plasma EFEMP1 levels and MRI markers of vascular brain injury and incident all-cause and Alzheimer’s disease (AD) dementia. Methods: We measured plasma EFEMP1 levels in 1597 [53% women, mean age 68.7 (SD 5.7) years] dementia-free Framingham Offspring cohort participants between 1998–2001 and subsequently followed them for incident dementia. Secondary outcomes included stroke, structural MRI brain measures and neurocognitive test performance. Results: During a median 11.8 [Q1, Q3 : 7.1, 13.3] year follow-up, 131 participants developed dementia. The highest quintile of plasma EFEMP1, compared to the bottom four quintiles, was associated with an increased risk of time to incident all-cause dementia (HR 1.77, 95% CI 1.18–2.64) and AD dementia (HR 1.76, 95% CI 1.11–2.81) but not with markers of vascular brain injury (WMH, covert brain infarcts or stroke). Higher circulating EFEMP1 concentrations were also cross-sectionally associated with lower total brain (β±SE, –0.28±0.11, p = 0.01) and hippocampal volumes (–0.006±0.003, p = 0.04) and impaired abstract reasoning (Similarities test, –0.18±0.08, p = 0.018 per standard deviation increment in EFEMP1). Conclusion: Elevated circulating EFEMP1 is associated with an increased risk of all-cause and AD dementia, smaller hippocampal and total brain volumes, and poorer cognitive performance. EFEMP1 may play an important biological role in the development of AD dementia. Further studies to validate these findings are warranted.

Characteristic Evaluation of Various Formulations of Anti-Aging Cream from Carotenoid Extract of Bacterial Symbiont Virgibacillus salarius Strain 19.PP.Sc1.6

Premature aging can be triggered by free radicals from UV rays, since exposure to these rays can cause the skin to experience oxidative stress. Oxidative stress induces intracellular DNA damage, protein denaturation, and lipid peroxidation that lead to cell death. However, cell death can be prevented with antioxidants such as carotenoids, which are among the potential natural compounds for its treatment. Sources of carotenoids include microbial symbionts associated with Sinularia sp., one of which is the bacterium Virgibacillus salarius strain 19.PP.Sc1.6, a carotenoid-producing bacteria. This study aims to explore the utilization of carotenoids from the bacterium V. salarius strain 19.PP.Sc1.6 for the preparation of anti-aging creams. Furthermore, the method employed three formulations (vs, ow, and wo) containing different types of cream tested for stability, and antioxidant and sunscreen abilities. The results obtained established that the carotenoid extract from V. salarius strain 19.PP.Sc1.6 was more stable in the cream vs. the oil-in-water type cream with an anionic emulsifier.

Senotherapeutic-like effect of Silybum marianum flower extract revealed on human skin cells

Cellular senescence causes irreversible growth arrest of cells. Prolonged accumulation of senescent cells in tissues leads to increased detrimental effects due to senescence associated secretory phenotype (SASP). Recent findings suggest that elimination of senescent cells has a beneficial effect on organismal aging and lifespan. In this study, using a validated replicative senescent human dermal fibroblasts (HDFs) model, we showed that elimination of senescent cells is possible through the activation of an apoptotic mechanism. We have shown in this replicative senescence model, that cell senescence is associated with DNA damage and cell cycle arrest (p21, p53 markers). We have shown that Silybum marianum flower extract (SMFE) is a safe and selective senolytic agent targeting only senescent cells. The elimination of the cells is induced through the activation of apoptotic pathway confirmed by annexin V/propidium iodide and caspase-3/PARP staining. Moreover, SMFE suppresses the expression of SASP factors such as IL-6 and MMP-1 in senescent HDFs. In a co-culture model of senescent and young fibroblasts, we demonstrated that senescent cells impaired the proliferative capacities of young cells. Interestingly, when the co-culture is treated with SMFE, the cell proliferation rate of young cells is increased due to the decrease of the senescent burden. Moreover, we demonstrated in vitro that senescent fibroblasts trigger senescent process in normal keratinocytes through a paracrine effect. Indeed, the conditioned medium of senescent HDFs treated with SMFE reduced the level of senescence-associated beta-galactosidase (SA-β-Gal), p16INK4A and SASP factors in keratinocytes compared with CM of senescent HDFs. These results indicate that SMFE can prevent premature aging due to senescence and even reprograms aged skin. Indeed, thanks to its senolytic and senomorphic properties SMFE is a candidate for anti-senescence strategies.