Abstract Stuttering is a complex speech disorder and heritability of this trait is persuasive, with multiple afflicted families showing phenotypic segregation across generations, yet no conclusive genetic etiology could be identified. Analyzing multiplex families using exome sequencing(ES) may help in identification of putative genes and scope for understanding the mutational burden for speech implicated pathways. In this study ES was performed in six individuals from two clinically well characterized, multiple affected, south Indian families (STU-65 and STU-66) showing stuttering across five generations. From ES to variant prioritization, a sequential bioinformatics approach was implemented to search for putative gene targets. In the two multiplex families studied, ES data analysis resulted in an enriched list of 14 genes (with variants) (COL4A2,COL6A3,COL6A6,ITGAX,LAMA5,ADAMTS9,CSGALNACT1, TMOD2,HTR2B,RSC1A1,TRPV2,WNK1,ARSD and SPTBN5) involved in neural functions. Additionally, a homozygous variant in NLRP11 gene and a heterozygous variant in NAGPA gene were identified in STU-65 family that needs further confirmation. Our results support the fact that stuttering is a polygenic disorder. The putative gene targets identified in our study can drive the research prospects to understand the underlying mechanisms. We hypothesize multiple and combined mechanisms to be involved in the genesis of stuttering. Keywords: Stuttering, exome sequencing, neural pathways

As percentages of elderly people rise in many societies, age-related diseases have become more prevalent. Research interests have been shifting to delaying age-related disease by delaying or reversing aging itself. We use metformin and rapamycin, two drugs at the center of anti-aging drug research, as an entry point to talk about important molecular and genetic anti-aging mechanisms that have been extensively studied with them, such as mTOR, AMPK, and epigenetic modifications. We also present a number of observational studies, animal studies, and clinical trials to reflect the potential and actual effects of the mechanisms. At the end, we list remaining concerns that not only apply to researches around metformin and rapamycin but also future researches to explore other anti-aging pathways and therapeutics.

The growing epidemic of many age-related chronic diseases, such as cardiovascular diseases, diabetes, cancer, and neurodegenerative diseases, especially Parkinson's and Alzheimer's disease, places an increasing burden on the healthcare systems worldwide. In recent years, efforts to manipulate the consequences of aging have yielded some success, and naturally, identifying effective ways to slow down or even reverse aging has become increasingly popular. Importantly, existing drugs can be repurposed for anti-aging effects. Studies from model organisms and early stage human clinical trials have found that metformin and rapamycin, which respectively are an effective anti-diabetic medication and an immunosuppressant, have promising results in slowing aging and treating age-related diseases. These findings point to the possibility that these two anti-aging drug candidates, and especially their derivatives which may reduce side effects, are likely to become the first genuine rejuvenation medications to achieve healthy aging. Here, we present knowledge on the mechanisms that are involved in the anti-aging effect of the two molecules, followed by an outline of a host of potential aging-related clinical applications. We finally provide insights on the considerations and further directions for the development of anti-aging drugs.