Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

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Despite decades of rigorous scientific endeavors for Alzheimer’s disease (AD) drug development, massive failures in clinical trials is continuously posing healthcare and societal burden. Currently recommended single targeted drugs including rivastigmine with limited bioavailability can alleviate AD symptoms only for a limited period of time but unable to reverse the disease progression. Recent evidences consider poly-pharmacological and multi-targeted agents aiming at amyloid and tau burden, neuroinflammation, neuroprotection and cognitive enhancement as potential treatment options. In this regard, bioactive herbal compounds with holistic action and minimal adversities have gained prominence, though lacunae in their scientific validation and limited bio-permeability to cross BBB represent major hurdles. Previously, we showed that lactoferrin conjugated PEG-S-S-PLA-PCL-OH efficaciously delivered herbal compounds to brain and such nano-herbal formulation of bacosides-lauric acid (BAN-LAN) attenuated neuronal damages induced by scopolamine in vitro. Here, we tested the preclinical potential of BAN-LAN in reversal of AD pathologies in 5XFAD transgenic mice. Our nano-herbal formulation substantially reduced amyloid burden by clearing Aβ plaques in the hippocampus of 5XFAD mice and also attenuated aβ42 induced alterations in AD associated gene expression in hippocampal neurons in vitro. It showed neuroprotection by rescuing neuronal damage and promoting neurogenesis in the hippocampus of AD transgenic mice. Anti-neuroinflammatory properties were also exhibited by the formulation as evident from inhibition of hippocampal astrocytic and microglial activation in 5XFAD mice. BAN-LAN showed cognitive efficacy by restoring memory impairment in AD transgenic mice and effects were more pronounced than unconjugated natural form and rivastigmine. These findings suggest that BAN-LAN may serve as a promising therapeutic agent for AD with better brain penetration and targeting multiple AD pathways.

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Tip-links as gating-spring in the mechanotransduction in hearing is still a debate. While the molecular elasticity of individual tip-link proteins warrants its candidature, the apparent rigidity from the heterotetrameric tip-links assembly refutes the claim. Using force-clamp experiments and simulations, we report that the heterotetrameric assembly is the natural selection for the gating-springs. Tip-links follow slip-ideal-slip bonds with increasing force. While in slip, the complex dissociates monotonously, ideal-bond interface responds indifferently to various auditory inputs. Insensitivity to forces renders tip-links as low-force pass filter, characteristic of gating-spring. Individual tip-links, however, forms slip-catch-slip bonds under tension. While catch bonds turn stronger with force from loud sound, our Langevin dynamics indicated the transition from slip-catch to slip-ideal bonds as cooperative effect of the dimers of individual protein complexes in tip-links. From molecular dynamics, we deciphered the molecular mechanism of catch bonds and its importance in deafness.

Background The emerging role of gut microbiota and their metabolites in the modulation of the gut-brain axis has received much attention as a new hope for the treatment of hard-to-treat chronic neurodegenerative diseases like Alzheimer’s Disease. The naturally occurring polyphenols can restore the gut-brain axis by modulating gut microbiota and brain neurotransmitters. However, the mechanism of action remained unclear. The Indian traditional medicine Triphala, a rich source of polyphenols, has been used on humans based on Prakriti or disease conditions for many years. Methods: In this study, the dual mode (morning and evening) action of Triphala was used to provide scientific evidence of its superior preventive and therapeutic efficacy in C57BL/6 and 5xFAD, APP/PS1 transgenic mouse model of Alzheimer’s disease. For behavior analysis, used the Morris water model and Y maze model to assess spatial memory and exploratory behavior. The blood serum and brain lysate were used to evaluate the inflammatory activity and oxidative parameters in the mice. The gut microbiome analysis was done by 16srRNA analysis from mice feces after 60 days of treatment. Results We observed that Triphala treatment has significantly improved cognitive function, by modulating the APP pathway, reducing inflammation, oxidative stress, and restoring the gut-brain axis by increasing the gut microbiota phyla of Bacteroides, Proteobacteria, Actinobacteria, etc., involved in maintaining the gut homeostasis. Conclusions Our study paved a new path for using dual modes of Triphala one or in combination to treat incurable AD.

Osteoarthritis (OA) is the fourth most debilitating multifactorial disease, associated with personal and socioeconomic burdens worldwide. Currently, no safe therapy is available that can effectively prevent the deterioration of cartilage and subchondral bone or reverse existing defects. To address this, we have designed a multitargeted formulation, PL02, consisting of standardized extracts of the Rosa canina L, and Hippophae rhamnoides, along with collagen peptide, to explore the pharmacological efficacy in the Monosodium iodoacetate-induced (MIA) OA model in the rodents. The results show oral administration of PL02 exhibits antioxidant effects via down-regulating NOS, alleviated pain-related behavior, and reduced inflammation via inhibiting IL-1b and dependent TNF-a production, downregulating CGRP1 and COX-II. PL02 exerted anti-catabolic and chondroprotective activity by significantly downregulating MMP13 and upregulating BCL2. PL02 exhibited chondrogenic activity by significantly upregulating SOX-9(master regulator of chondrogenesis), Coll-I, and aggrecan, the major collagen and proteoglycan in the articular cartilage and prevented microarchitectural deterioration of subchondral bone. Thus, orally active PL02, a multi-targeted disease-modifying therapy that has not only alleviated pain and inflammation but also effectively arrested cartilage, and subchondral bone deterioration, constitutes a safe novel candidate for OA treatment and management.