Potential approaches for intervening aging

Abstract

Though immortality and regeneration were ludicrous and far-fetched in an age of ignorance and superstition, people have never stopped looking for the elixir of longevity. As a result of advancements in lifestyle and medical care, the average human life expectancy has risen in recent decades, along with the increasingly higher incidence of aging-related diseases. With the advance in biological techniques, our understanding of aging and aging-related diseases has expanded significantly. Molecular and cellular mechanisms that contribute to the aging process and age-related diseases can be classified into several categories, including genomic instability, telomere atrophy, epigenetic changes, loss of protein stability, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell depletion, and impaired intercellular communication [1].Along with the diverse strategies that have been exploited to explain aging, our ideas of aging intervention have also grown rapidly and multiple potentially effective strategies have been investigated. Here, we summarize these approaches below, dividing them into the following categories: (1) pharmacological administration; (2) gene therapy; (3) regenerative medicine; and (4) immunogenic intervention. Pharmacological administrationSenescent cells release enormous amounts of inflammatory cytokines, immunomodulators, growth factors and proteases, which are known as senescence-associated secretory phenotypes (SASP). Exosomes and episomes carrying enzymes, microRNAs, DNA fragments, chemokines, and other physiologically active components can also be found in the SASP [2]. Given that SASP and SASP-secreting cells have been regarded as possible therapeutic targets to ameliorate inflammatory conditions in the elderly, senolytics referred to the agents that selectively kill senescent cells are gaining traction as a way to possibly slow down the aging process and ameliorate organ malfunction. As such, the first empirical senolytic combination that extends mouse lifespan includes dasatinib, originally developed to target oncogene-addiction in leukemia, and quercetin, which inhibits the mTOR pathway, among numerous others [3]. In humans, dasatinib 100 mg