Trends in Endocrinology & Metabolism
ReviewFeature ReviewCellular and molecular longevity pathways: the old and the new
Section snippets
Pathways that control longevity across species: known mechanisms and new findings
Aging is a complex process defined as progressive functional deterioration associated with frailty, disease, and death. Over the past decades numerous genes and conditions have been revealed to influence aging across taxa. Among the most comprehensively studied pathways are the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway and dietary restriction (DR, see Glossary). In this review we focus on recently identified mechanisms influencing longevity, aiming to provide an
Genome integrity and stability
Accumulating evidence indicates that aging is accompanied by an increase in genome damage and instability [47]. In support of this notion, numerous progeroid diseases, rare genetic disorders that mimic physiological aging, such as the Werner and Bloom syndromes among others, have been associated with accumulated genomic damage [48]. Damage occurs during the course of a lifetime due to extrinsic or intrinsic causes: the former include environmental insults of physical, chemical or biological
Stem cells and their niche during aging
Adult or tissue stem cells represent small and quiescent populations that are present in multiple tissues, and thus can specifically regenerate the cells of the tissue they belong to. In this way, they largely determine the ability of tissues to regenerate not only during the normal wear and tear but also in response to injury. Stem cell self-renewal, maintenance, and differentiation are ultimately regulated by the integration of local and systemic signals with intrinsic factors that determine
Immunity, inflammation, and microbiota in aging: the good, the bad, and the ugly
During aging, innate and adaptive immune responses gradually deteriorate, leading to immunosenescence. Upon invasion of pathogenic organisms, innate immunity is triggered as the first line of defense, through pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and cytoplasmic receptors, which recognize pathogen-associated molecular patterns (PAMPs). Innate immune responses are followed and complemented by the activation of the adaptive immune system, particularly when
Proteostasis-related stress response pathways: Dr Jekyll or Mr Hyde?
One of the major hallmarks of aging is the loss of proteostasis, allowing damaged proteins and organelles to accumulate, leading to diverse pathologies. The sophisticated machineries that restore protein homeostasis and normal cellular and organismal function become compromised during aging, leading to adverse outcomes including cell death. Some of these housekeeping mechanisms include the stress response pathways, the autophagy–lysosomal machinery. and the ubiquitin–proteasome system (UPS)
Concluding remarks and future perspectives
Driven by changing demographics in the recent decades, the field of aging has built up solid resources to investigate the mechanisms that control longevity. These include experimental models from different phyla, including in particular S. cerevisiae, C. elegans, D. melanogaster, rodents, and primates. Based on these models, several signaling pathways have been identified that control aging in a well-conserved fashion across the evolutionary spectrum, such as the insulin and TOR signaling
Acknowledgments
We apologize to those colleagues whose work could not be referenced directly owing to space constraints. V.N. is supported by a European Molecular Biology Organization (EMBO) long-term fellowship. E.K. is supported by the General Secretariat for Research and Technology of the Greek Ministry of Education. Work in the authors’ laboratory is also funded by grants from the European Research Council (ERC) and the European Commission 7th Framework Program.
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