By 2030 almost every fourth person will be 65 or older in Switzerland, Europe, and USA [1,2]. Since old age is the main risk factor for developing cancer, neurodegenerative, cardiovascular, and metabolic diseases, as well as other age-related pathologies (Fig. 1), the growing elderly population poses an immense social burden on our younger generations and a financial burden on our healthcare system. It has been calculated that in the US delaying the onset by two years of these diseases would save $7.1 trillion over the next fifty years . The onset of these diseases varies because the rate of aging is plastic and is influenced by environmental and genetic factors [4-6]. For instance, people who live beyond 100 years (centenarians) spend most of their lives in good health with rapid decline only towards the end of life . Importantly, centenarians carry polymorphisms in genes that have been discovered in model organisms, such as the nematode Caenorhabditis elegans, to extend healthspan (the period of life spent in good heath) and lifespan . To understand the causal relationships between genes and healthy aging, C. elegans is indeed a pioneering system to model the aging process because of its ease for genetic manipulation, high evolutionary conservation of genes implicated in human diseases , and short lifespan (3 weeks). Importantly, using C. elegans lifespan assays as a read-out for extension of healthspan is a tractable and fast approach for discovering novel mechanisms that confer healthy aging. Several fundamental mechanisms discovered in C. elegans have been shown to delay age-related pathologies in higher organisms, such as mice, and these mechanisms have major implications for humans aging [6,10-21]. Hence, by using C. elegans to model the aging process we could rapidly identify strategies to improve human healthspan.
Fig.1. The goal of aging research is to extend human healthspan. Left panel shows average human lifespan (black line) and the rate of disease onset (red line). Delaying age-dependent diseases (dashed red line) would improve healthy aging (dashed green line). Right panel depicts disease free time (healthspan) and the problem of co-morbidities at the end of life for the average human population and centenarians . Eliminating one disease will only slightly increase healthspan because of other age-dependent diseases. Our mission is to identify strategies that extend healthspan.
1. UN Population, WHO. at <www.unpopulation.org>
2. Trippel, M. & Groth, H. Demographic Shifts in EU 27, Norway and Switzerland: Population and Dependency Ratio Forecasts until 2030. World Demographic & Ageing Forum 1–12 (2011).
3. Goldman, D. P. et al. Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Aff (Millwood) 32, 1698–1705 (2013).
4. Kenyon, C. J. The genetics of ageing. Nature 464, 504–512 (2010).
5. López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194–1217 (2013).
6. Partridge, L. Intervening in ageing to prevent the diseases of ageing. Trends Endocrinol Metab 25, 555–557 (2014).
7. Andersen, S. L., Sebastiani, P., Dworkis, D. A., Feldman, L. & Perls, T. T. Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span. J Gerontol A Biol Sci Med Sci 67, 395–405 (2012).
8. Pawlikowska, L. et al. Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. Aging Cell 8, 460–472 (2009).
9. Shaye, D. D. & Greenwald, I. OrthoList: a compendium of C. elegans genes with human orthologs. PLoS ONE 6, e20085 (2011).
10. Ristow, M. & Schmeisser, K. Mitohormesis: Promoting health and lifespan by increased levels of reactive oxygen species (ROS). Dose Response 12, 288–341 (2014).
11. Harrison, D. E. et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395 (2009).
12. Vellai, T. et al. Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426, 620–620 (2003).
13. Blagosklonny, M. V. & Hall, M. N. Growth and aging: a common molecular mechanism. Aging (Albany NY) 1, 357–362 (2009).
14. Mannick, J. B. et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med 6, 268ra179–268ra179 (2014).
15. Houtkooper, R. H., Pirinen, E. & Auwerx, J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol 13, 225–238 (2012).
16. Kennedy, B. K. et al. Geroscience: linking aging to chronic disease. Cell 159, 709–713 (2014).
17. Guarente, L. Aging research-where do we stand and where are we going? Cell 159, 15–19 (2014).
18. Edifizi, D. & Schumacher, B. Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms. Biomolecules 5, 1855–1869 (2015).
19. Yu, S. & Driscoll, M. EGF signaling comes of age: promotion of healthy aging in C. elegans. Exp Gerontol 46, 129–134 (2011).
20. Driscoll, M. & Gerstbrein, B. Dying for a cause: invertebrate genetics takes on human neurodegeneration. Nat Rev Genet 4, 181–194 (2003).
21. Onken, B. & Driscoll, M. Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1. PLoS ONE 5, e8758 (2010).
22. Figure 1 modified from M. Collins and W. Mair.