Lifespan of the versatile model system Caenorhabditis elegans can be extended by a decrease of insulin/IGF‑1 signaling, TOR signaling, mitochondrial function, protein synthesis and dietary intake. The exact molecular mechanisms by which these modulations confer increased life expectancy are yet to be determined but increased stress resistance and improved protein homeostasis seem to be of major importance. In this chapter, we explore the interactions among several genetic pathways and cellular functions involved in lifespan extension and their relation to protein homeostasis in C. elegans. Several of these processes have been associated, however some relevant data are conflicting and further studies are needed to clarify these interactions. In mammals, protein homeostasis is also implicated in several neurodegenerative diseases, many of which can be modeled in C. elegans.
Oncogenic and environmental (reactive oxygen species, UV, etc.) stresses can induce premature cellular senescence without critical telomere shortening. The role of the Ras/Raf/ERK signal transduction cascade in this process has been previously established, but recent evidence also indicates a...
Aging is a process in which individuals undergo an exponential decline in vitality, leading to death. In the last two decades, the study of the molecular regulation of aging in model organisms, particularly in C. elegans, has greatly expanded our knowledge of aging. Multiple longevity...
Alterations in the rate and extent of protein synthesis, accuracy, posttranslational modifications and turnover are among the main molecular characteristics of aging. A decline in the cellular capacity through proteasomal and lysosomal pathways to recognize and preferentially degrade damaged...
SUMOylation is a reversible posttranslational modification, where a small peptide (SUMO) is covalently attached to a target protein and changes its activity, subcellular localization and/or interaction with other macromolecules. SUMOylation substrates are numerous and diverse and modification...
The animal’s ability to maintain homeostasis in response to different environments can influence its survival. This chapter will discuss the mechanisms by which environmental cues act through sensory pathways to influence hormone secretion and homeostasis. Interestingly, recent studies also...
The stability of the proteome is crucial to the health of the cell, and contributes significantly to the lifespan of the organism. Aging and many age‑related diseases have in common the expression of misfolded and damaged proteins. The chronic expression of damaged proteins during disease...
Autophagy is an evolutionarily conserved process essential for cellular homeostasis and organismal viability. In fact, this pathway is one of the major protein degradation mechanisms in eukaryotic cells. It has been repeatedly reported that the autophagic activity of living cells decreases...
Lifespan of the versatile model system Caenorhabditis elegans can be extended by a decrease of insulin/IGF‑1 signaling, TOR signaling, mitochondrial function, protein synthesis and dietary intake. The exact molecular mechanisms by which these modulations confer increased life expectancy are...
Ubiquitination of endogenous proteins is one of the key regulatory steps that guides protein degradation through regulation of proteasome activity. During the last years evidence has accumulated that proteasome activity is decreased during the ageing process in various model systems and that...
Preserving the integrity of proteins, biomolecules prone to molecular damage, is a fundamental function of all biological systems. Impairments in protein quality control (PQC) may lead to degenerative processes, such as aging and various disorders and diseases. Fortunately, cells contain a...
Appropriate regulation of mRNA translation is essential for growth and survival and the pathways that regulate mRNA translation have been highly conserved throughout eukaryotic evolution. Translation is controlled by a complex set of mechanisms acting at multiple levels, ranging from global...
In this chapter we review the different technologies that can be applied in the analysis of protein homeostasis and metabolism in ageing research. Special focus will be on technologies with a potential to circumvent the problems associated with cell heterogeneity in biomarker discovery. Often...
Cellular homeostasis, which is needed for the cells to survive, requires a well‑controlled balance in protein turnover. Both protein synthesis and degradation are influenced by distinct genetic pathways that control aging in divergent eukaryotic species. These conserved mechanisms involve...
Homeostasis is a key feature of cellular lifespan. Maintenance of cellular homeostasis influences the rate of aging and its efficiency is determined by the cooperation between protein stability and resistance to stress, protein refolding, protein repair and proteolysis of damaged proteins....
Growth and somatic maintenance are thought to be antagonistic pleiotropic traits, but the molecular basis for this tradeoff is poorly understood. Here it is proposed that changes in protein synthesis mediate the tradeoffs that take place upon genetic and environmental manipulation in various...
Muscle ageing is characterized by a decline in functional performance and restriction of adaptability, due to progressive loss of muscle tissue coupled with a decrease in strength and force output. Together with selective activation of apoptotic pathways, a hallmark of age‑related muscle...