Abstract
Aging represents a significant biological process having strong associations with cancer, diabetes, and neurodegenerative and cardiovascular disorders, which leads to progressive loss of cellular functions and viability. Astonishingly, age-related disorders share several genetic and molecular mechanisms with the normal aging process. Over the last three decades, budding yeast Saccharomyces cerevisiae has emerged as a powerful yet simple model organism for aging research. Genetic approaches using yeast RLS have led to the identification of hundreds of genes impacting lifespan in higher eukaryotes. Numerous interventions to extend yeast lifespan showed an analogous outcome in multi-cellular eukaryotes like fruit flies, nematodes, rodents, and humans. We collected and analyzed a multitude of observations from published literature and provide the contribution of yeast in the understanding of aging hallmarks most applicable to humans. Here, we discuss key pathways and molecular mechanisms that underpin the evolutionarily conserved aging process and summarize the current understanding and clinical applicability of its trajectories. Gathering critical information on aging biology would pave the way for future investigation targeted at the discovery of aging interventions.
Highlights
Aging is a multifactorial, highly complex biological process that results in compromised physiological functions
Histone acetylation is associated with actively transcribed chromatin, and its global decline is associated with aging in human diploid fibroblasts [81] and aged rodent brains [82]
These reports suggested that a conserved target of rapamycin (TOR) pathway modulates cell growth metabolism and functions in the regulation of longevity in organisms ranging from yeast to humans
Summary
Highly complex biological process that results in compromised physiological functions. We discuss our current understanding of the dynamic and conserved nature of aging-associated putative molecular mechanisms in divergent organisms with a focus on yeast and humans (Figure 1) and highlight the conserved longevity pathways and age-associated genes. Resilient aggregates of proteins are found to increase in aged yeast cells The defects in this normal pathway represent dysfunctions in protein homeostasis. Conserved subunits of proteostasis pathway share common functions across eukaryotes and play divergent roles in aging mechanisms in human pathologies. Yeast histone deacetylase Sir (silent information regulator) is highly conserved and extensively studied for its role in lifespan extension [38].
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