Table 1.

Current approaches in aging research, the insights they provide and their advantages and limitations

Name	Taxa	Insights	Advantages	Limitations
Targeted genetic modifications	Established laboratory models (yeast, Drosophila, C. elegans, mice), wider range with recent development of CRISPR‐Cas (1)	Biochemical pathways and molecular targets for drug development (e.g., TOR and rapamycin (2))	Opportunity to test the effects of single‐gene manipulations against a fixed genetic background	A fixed genetic background can have profound effects on the phenotypic outcome of a given intervention (3), but see also (4,5) for the use of diverse genetic background)
Comparative genomics of long‐lived animals	Naked mole rats, bluefin whale and other long‐lived species	Genomic variations related to cellular mechanisms that facilitate protection against aging‐related declines (6)	Identification of shared genomic associations with long lifespan	Difficulty of disentangling longevity from other unusual species characteristics, such as eusociality or adaptation to subterranean life
Cross‐sectional analyses of survival in wild populations	Mammals, birds, dragonflies	Specific challenges important to patterns of mortality under natural conditions (e.g., elevated risk of predation or bouts of mortality under particularly challenging environmental conditions) (7,8)	Clear identification of evolutionarily relevant sources of mortality and their timing, and estimates of gene‐by‐environment interactions	Low (if any) replication across populations, comparisons often made at the individual level within a single population (9,10) or between closely related species (8)
Transcriptional and genetic association studies	Humans	Significant general association of APOE and FOXOA3 gene polymorphisms with long life (11); large population‐specificity in other aging‐related polymorphisms (12)	Large‐scale longitudinal data in replicated natural populations, often including details on functional declines	Insight into proximate mechanisms, but not directly into the evolution of aging
Experimental evolution	Short‐lived laboratory animals (Callosobruchus, Caenorhabditis, Drosophila)	Demonstrating the capacity of specific organisms to respond to selection favoring increased or decreased rates of aging (13,14)	Maintains associated trade‐offs in other life‐history traits	Commonly excludes tests of trade‐offs in response to challenging environment (but see (14)); lab‐adapted populations difficult to associate with natural settings; limited to short‐lived nonvertebrates
Common garden experiments	Various taxa that can be kept in captivity	Revealing genetically‐determined interpopulation variation in aging traits	Standardization of environmental hazards; use of replicated natural populations	More complicated designs are needed to exclude population‐specific adaptations matching specific lab conditions (e.g., ambient temperature)

References: (1) Harel et al. (2015); (2) López‐Otín et al. (2013); (3) Liao et al. (2010); (4) Harrison et al. (2009); (5) Lind et al. (2016); (6) Fang et al. (2014); (7) Hayward et al. (2011); (8) Wilson et al. (2007); (9) Massot et al. (2011); (10) Sharp and Clutton‐Brock (2011); (11) Deelen et al. (2011); (12) Beekman et al. (2013); (13) Stearns et al. (2000); (14) Chen and Maklakov (2012).