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1.
Mol Psychiatry ; 27(4): 1936-1944, 2022 04.
Article in English | MEDLINE | ID: covidwho-1683976

ABSTRACT

The world population is getting older and studies aiming to enhance our comprehension of the underlying mechanisms responsible for health span are of utmost interest for longevity and as a measure for health care. In this review, we summarized previous genetic association studies (GWAS) and next-generation sequencing (NGS) of elderly cohorts. We also present the updated hypothesis for the aging process, together with the factors associated with healthy aging. We discuss the relevance of studying older individuals and build databanks to characterize the presence and resistance against late-onset disorders. The identification of about 2 million novel variants in our cohort of more than 1000 elderly Brazilians illustrates the importance of studying highly admixed populations of non-European ancestry. Finally, the ascertainment of nonagenarians and particularly of centenarians who were recovered from COVID-19 or remained asymptomatic opens new avenues of research aiming to enhance our comprehension of biological mechanisms associated with resistance against pathogens.


Subject(s)
COVID-19 , Longevity , Aged , Aged, 80 and over , Brazil , Cohort Studies , Genetic Association Studies , Humans , Longevity/genetics
2.
Cells ; 11(3)2022 01 29.
Article in English | MEDLINE | ID: covidwho-1667056

ABSTRACT

Epigenetic alterations pose one major hallmark of organismal aging. Here, we provide an overview on recent findings describing the epigenetic changes that arise during aging and in related maladies such as neurodegeneration and cancer. Specifically, we focus on alterations of histone modifications and DNA methylation and illustrate the link with metabolic pathways. Age-related epigenetic, transcriptional and metabolic deregulations are highly interconnected, which renders dissociating cause and effect complicated. However, growing amounts of evidence support the notion that aging is not only accompanied by epigenetic alterations, but also at least in part induced by those. DNA methylation clocks emerged as a tool to objectively determine biological aging and turned out as a valuable source in search of factors positively and negatively impacting human life span. Moreover, specific epigenetic signatures can be used as biomarkers for age-associated disorders or even as targets for therapeutic approaches, as will be covered in this review. Finally, we summarize recent potential intervention strategies that target epigenetic mechanisms to extend healthy life span and provide an outlook on future developments in the field of longevity research.


Subject(s)
Epigenomics , Longevity , Aging/genetics , DNA Methylation/genetics , Epigenesis, Genetic , Humans , Longevity/genetics
3.
Molecules ; 26(7)2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1167670

ABSTRACT

Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withaniasomnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.


Subject(s)
Antidepressive Agents/pharmacology , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Aging/drug effects , Aging/physiology , Animals , Antioxidants/pharmacology , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Gene Knockout Techniques , Heat-Shock Response/drug effects , Longevity/drug effects , Longevity/genetics , Longevity/physiology , Mutation , Osmotic Pressure/drug effects , Oxidative Stress/drug effects , Plant Extracts/chemistry , Reactive Oxygen Species/metabolism
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