Aging is the process underlying the progressive structural and functional decline with age that affects nearly every known biological entity; first, leading to increased extrinsic mortality risk (disease, predation, accident), and finally, inescapable death. The considerable social and economical impact of human aging has incited great efforts in elucidating how we age and what can be done about it. Although substantial progress has been made, a conclusive mechanistic model that explains in detail how cells, tissues, and organs gradually start to break down once adulthood is reached, is still lacking.In general, the aging process is studied by using model organisms, ranging from unicellular yeasts and invertebrate species such as the fruitfly and nematode (e.g. C. elegans), up to mammalian species, including mice, rats and primates. Using such model organisms has revealed several genetic and environmental interventions that can successfully slow down the aging process in these animals. Reduced insulin-like signaling and dietary restriction are two prime examples of such interventions. These interventions have in common that they rely on a complex network of interconnecting regulatory pathways inside cells that intercept, integrate and transduce signals from the environment towards the nucleus where they can induce an extensive genetic response. This altered gene expression is then translated in the production of proteins and enzymes that are part of fundamental biological processes, such as energy metabolism, protein synthesis and degradation, stress-related defense and detoxification.The nematode model system Caenorhabditis elegans has proven ideal for aging research for several reasons. Its short generation time and lifespan allows fast and repeatable screening for long-lived mutants and conditions. In addition, an impressive number of mutant C. elegans strains is available, several of which are long-lived. The C. elegans genome has been fully sequenced and is well-annotated which has allowed and facilitated the development and use of numerous genetic tools. In this thesis we have used the nematode C. elegans to chart the changes that occur at the expression level of proteins (the proteome) in response to reduced signaling through the insulin/insulin-like growth factor1 (IGF1) cascade (daf-2 mutant) as well as dietary restriction (DR), two interventions that appear to operate via genetically separable signaling cascades and extend lifespan through partially independent mechanisms. A popular approach to identify the downstream effectors of age-associated signaling cascades in many previous studies has been to generate and compare genome-wide transcript profiles (the transcriptome). However, messenger RNAs (mRNAs) are not the actual players in biological processes and the quantitative correlation between gene transcript and final protein product is often lacking. Therefore, direct estimates of protein abundance levels provide a much clearer view on molecular alterations of cell physiology that correlate to longevity. Although bacterial dilution-induced DR and reduced insulin-like signaling extend lifespan through parallel signaling pathways, we reasoned that the generated proteome profiles would reveal common alterations in cellular physiology that are potentially required for longevity in these worms. In this study, attenuation of protein synthesis was identified as one such candidate process. This finding is significant since it was previously known that experimentally enforced partial inhibition of overall protein synthesis extends C. elegans lifespan and increases stress-resistance. We argue that the inhibition of mRNA translation is only one part of a general activation of stress-defensive systems in the daf-2 mutant. Using classic radioactive pulse-chase experiments we also show that global protein degradation is unchanged in DR, but appears drastically decreased in daf-2 mutants. This decrease in protein turnover (degradation and synthesis) invalidates the protein turnover longevity hypothesis which predicted increased turnover of proteins in long-lived organisms.In addition to a boost in stress-resistance, the proteome profile of daf-2 also indicates a drastic restructured energy metabolism, reminiscent to that of hypometabolic and developmentally arrested dauer larvae. Energy metabolism in daf-2 is tuned for efficient and economical utilization of internal carbohydrate and lipid nutrient reserves, possibly also shunting metabolites through alternative energy-generating pathways. These adaptations are likely necessary to allow long-time survival under conditions of low food availability. The proteome profile of long-lived worms was also characterized by the increased abundance of many muscle-related proteins, which was shown to be the result of a relative increase in the biomass of (body-wall) muscle tissue in these worms. In addition, daf-2 actively invests in maintaining muscle integrity by stimulating gene expression of structural muscle constituents and possibly also by maintaining protein synthesis limited to the muscle. Therefore, C. elegans protects its muscles from catabolism under conditions normally associated with extensive atrophy in vertebrates. Sustained locomotion in harsh environments is evolutionary advantageous since it allows scouting for food or invertebrate carriers and escaping stressfull conditions that stall development. Autophagy is a major cellular catabolic process conserved in all eukaryotic cells involving the degradation and recycling of cellular material and organelles by numerous acid hydrolases in the lysosomal system. This process is required in several long-lived mutants (such as daf-2) and lifespan extending interventions (such as DR). Its beneficial effect on lifespan is thought to arise from preventing the accumulation of intracellular damage by increasing global turnover of old and damaged macromolecules (e.g. proteins) and organelles. However, as mentioned above, this explanation is unlikely. The lysosome contains dozens of distinct hydrolases involved in the degradation and processing of undefined lipophilic and protein substrates, but their exact role is seldom known. In a pilot study aimed at finding the important enzymes responsible for autophagy-induced lifespan extension, extensive, but complex regulation in gene expression of numerous lipid, protein and other catabolic hydrolases was shown, indicative for a wide functional diversity among these enzymes. Consistent with reduced protein turnover, preliminary evidence also suggests a possible general repression of lysosomal activity in the daf-2 mutant. In conclusion, a clear pattern emerged from the daf-2 proteome profile, indicating that these mutants reside in a conservative state, characterized by keeping metabolic expenses low (hypometabolic) and stress-defenses high. Consistent with this paradigm, we have shown that costly protein turnover is most likely decreased in long-lived worms, a finding that clashes with established viewpoints on damage-centered aging theories.