Relating aging and autophagy: a new perspective towards the welfare of human health.

The most common factor that contributes to aging is the loss of proteostasis, resulting in an excess amount of non-functional/damaged proteins. These proteins lead to various age-associated phenotypes such as cellular senescence and dysfunction in the nutrient-sensing pathways. Despite the various factors that can contribute to aging, it is still a process that can be changed. According to recent advances in the field of biology, the ability to alter the pathways that are involved in aging can improve the lifespan of a person. Autophagy is a process that helps in preserving survival during stressful situations, such as starvation. It is a common component of various anti-aging interventions, including those that target the insulin/IGF-1 and rapamycin signaling pathways. It has been shown that altered autophagy is a common feature of old age and its impaired regulation could have significant effects on the aging process. This review aims to look into the role of autophagy in aging and how it can be used to improve one's health.

Aza-phenol Based Macrocyclic Probes Design for "CHEF-on" Multi Analytes Sensor: Crystal Structure Elucidation and Application in Biological Cell Imaging.

Metal bound macrocyclic compounds found in biological systems inspired us to design and synthesize two Robson-type macrocyclic Schiff-base chemosensors, H 2 L1 (H 2 L1=1,11-dimethyl-6,16-dithia-3,9,13,19-tetraaza-1,11(1,3)-dibenzenacycloicosaphane-2,9,12,19-tetraene-1,11-diol) and H 2 L2 (H 2 L2=1,11-dimethyl-6,16-dioxa-3,9,13,19-tetraaza-1,11(1,3)-dibenzenacycloicosaphane-2,9,12,19-tetraene-1,11-diol). Both the chemosensors have been characterized with different spectroscopic techniques. They act as multianalyte sensor and exhibit "turn-on" fluorescence toward different metal ions in 1X PBS (Phosphate Buffered Saline) solution. In presence of Zn2+, Al3+, Cr3+ and Fe3+ ions, H 2 L1 exhibits ∼6-fold enhancement of emission intensity, while H 2 L2 shows ∼6-fold enhancement of emission intensity in the presence of Zn2+, Al3+ and Cr3+ ions. The interaction between the different metal ion and chemosensor have been examined by absorption, emission, and 1H NMR spectroscopy as well as by ESI-MS+ analysis. We have successfully isolated and solved the crystal structure of the complex [Zn(H 2 L1)(NO3)]NO3 (1) by X-ray crystallography. The crystal structure of 1 shows 1:1 metal:ligand stoichiometry and helps to understand the observed PET-Off-CHEF-On sensing mechanism. LOD values of H 2 L1 and H 2 L2 toward metal ions are found to be ∼10-8 and ∼10-7 M, respectively. Large Stokes shifts of the probes against analytes (∼100 nm) make them a suitable candidate for biological cell imaging studies. Robson type phenol based macrocyclic fluorescence sensors are very scarce in the literature. Therefore, the tuning of structural parameters as the number and nature of donor atoms, their relative locations and presence of rigid aromatic groups can lead to the design of new chemosensors, which can accommodate different charged/neutral guest(s) inside its cavity. The study of the spectroscopic properties of this type of macrocyclic ligands and their complexes might open a new avenue of chemosensors.

Two rhodamine-azo based fluorescent probes for recognition of trivalent metal ions: crystal structure elucidation and biological applications.

Two rhodamine and azo based chemosensors (HL1 = (3',6'-bis(ethylamino)-2-((2-hydroxy-3-methoxy-5-(phenyldiazenyl)benzylidene)amino)-2',7'-dimethylspiro[isoindoline-1,9'-xanthen]-3-one) and HL2 = (3',6'-bis(ethylamino)-2-(((2-hydroxy-3-methoxy-5-(p-tolyldiazenyl)benzylidene)amino)-2',7'-dimethylspiro[isoindoline-1,9'-xanthen]-3-one) have been synthesized for colorimetric and fluorometric detection of three trivalent metal ions, Al3+, Cr3+ and Fe3+. The chemosensors have been thoroughly characterized by different spectroscopic techniques and X-ray crystallography. They are non-fluorescent due to the presence of a spirolactam ring. The trivalent metal ions initiate an opening of the spirolactam ring when excited at 490 nm in Britton-Robinson buffer solution (H2O/MeOH 1 : 9 v/v; pH 7.4). The opening of the spirolactam ring increases conjugation within the probe, which is supported by an intense fluorescent pinkish-yellow colouration and an enhancement of the fluorescence intensity of the chemosensors by ∼400 times in the presence of Al3+ and Cr3+ ions and by ∼100 times in the presence of Fe3+ ions. Such a type of enormous fluorescence enhancement is rarely observed in other chemosensors for the detection of trivalent metal ions. A 2 : 1 binding stoichiometry of the probes with the respective ions has been confirmed by Job's plot analysis. Elucidation of the crystal structures of the Al3+ bound chemosensors (1 and 4) also justifies the 2 : 1 binding stoichiometry and the presence of an open spirolactam ring within the chemosensor framework. The limit of detection (LOD) values for both the chemosensors towards the respective metal ions are in the order of ∼10-9 M which supports their application in the biological field. The biocompatibility of the ligands has been studied with the help of the MTT assay. The results show that no significant toxicity was observed up to 100 µM of chemosensor concentration. The capability of our synthesized chemosensors to detect intracellular Al3+, Cr3+ and Fe3+ ions in the cervical cancer cell line HeLa was evaluated with the aid of fluorescence imaging.

Aza-Crown-Based Macrocyclic Probe Design for "PET-off" Multi-Cu2+ Responsive and "CHEF-on" Multi-Zn2+ Sensor: Application in Biological Cell Imaging and Theoretical Studies.

The work represents a rare example of an aza-crown-based macrocyclic chemosensor, H2DTC (H2DTC = 1,16-dihydroxy-tetraaza-30-crown-8) for the selective detection of both Zn2+ and Cu2+ in HEPES buffer medium (pH 7.4). H2DTC exhibits a fluorescence response for both Zn2+ and Cu2+ ions. The reversibility of the chemosensor in its binding with Zn2+ and Cu2+ ions is also examined using a Na2EDTA solution. H2DTC exhibits a chelation-enhanced fluorescence (CHEF) effect in the presence of Zn2+ ions and a quenching effect (CHEQ) in the presence of paramagnetic Cu2+ ions. Furthermore, the geometry and spectral properties of H2DTC and the chemosensor bound to Zn2+ have been studied by DFT and TDDFT calculations. The limit of detection (LOD) values are 0.11 × 10-9 and 0.27 × 10-9 M for Cu2+ and Zn2+, respectively. The formation constants for the Zn2+ and Cu2+ complexes have been measured by pH-potentiometry in 0.15 M NaCl in 70:30 (v:v) water:ethanol at 298.1 K. UV-vis absorption and fluorometric spectral data and pH-potentiometric titrations indicate 1:1 and 2:1 metal:chemosensor species. In the solid state H2DTC is able to accommodate up to four metal ions, as proved by the crystal structures of the complexes [Zn4(DTC)(OH)2(NO3)4] (1) and {[Cu4(DTC)(OCH3)2(NO3)4]·H2O}n (2). H2DTC can be used as a potential chemosensor for monitoring Zn2+ and Cu2+ ions in biological and environmental media with outstanding accuracy and precision. The propensity of H2DTC to detect intracellular Cu2+ and Zn2+ ions in the triple negative human breast cancer cell line MDA-MB-468 and in HeLa cells has been determined by fluorescence cell imaging.