Aging is affected by biological and social determinants (1). Biological determinants involve physiological changes associated with aging (e.g., telomere length) (1). Social determinants involve the experiences of individuals during life (e.g., socioeconomic status) (1). With an increasing aging population, it is important to understand the social factors that influence healthy aging (2). Cho et al. use the fruit fly, Drosophila melanogaster, to explore the social determinant of housing by cohabitating old flies with young flies (3).
Housing and social isolation are important social factors to consider (2). Both financial stress and familial loss associated with age can negatively impact aging populations (2). A strategy to combat these factors is intergenerational housing, the cohousing of older individuals with younger individuals (2). Many universities, including McMaster University, have pursued programs involving intergenerational housing (4).
While using Drosophila may seem unusual to investigate intergenerational housing, they are perceptive organisms. Drosophila can sense their surroundings through olfactory and gustatory pathways (3). In social isolation models of Drosophila, sleep and food intake was dysregulated (5). To explore the benefit of intergenerational housing, Cho et al. pair old and young flies and measure health during aging (3).
Old flies (40 days old) were placed with young flies (1 day old) and cohoused for the remainder of their lives (Figure 1) (3). When kept in a ratio of one old fly to three young flies, the lifespan of old flies was extended (3). If the density of young flies was increased (one old fly to nine young flies), there was an even greater extension of lifespan in male flies (Figure 1) (3). Interestingly, there appeared to be a limit to this lifespan-increasing ability of young flies; when the young flies were replaced with a new group every seven days, the lifespan of old flies was not as extended when compared to keeping the original group of young flies (3).
This lifespan extension led Cho et al. to explore the physiological health of the flies (3). Old flies cohoused with young flies for 20 days had better motility ability and stress resistance (3). Protein expression showed that Ref.P and Atg8a, proteins known to extend lifespan through autophagy activation, were increased in old flies cohoused with young flies for 20 days (3). These old flies also saw a decreased expression of ubiquitinated histone 2 A, a marker for aging (3).
Cho et al. desired to elucidate the mechanism for lifespan extension. Given the known role of olfactory and gustatory sensing in flies, the authors chose to target these pathways (3). To remove the olfactory and gustatory senses, flies with a mutated odorant receptor gene (or83b) or gustatory-specific cation channel gene (ppk23) were used, respectively (3,6). Both old orb83b and ppk23 mutant flies (60 days old as mutant flies live longer) did not have a significantly extended lifespan when cohoused with young flies in a ratio of one old fly to three young flies (Figure 1) (3). As the lifespan-extension effects are blunted when the olfactory and gustatory pathways are inhibited, it implies that these pathways have a role in perceiving young flies (3). Interestingly, there was a lifespan-extension effect when the density of young flies was increased (one old fly to nine young flies) (3). This result implies that other pathways may also be important for sensing young flies.
An interesting aspect of this paper is sex differences. In multiple experiments (e.g., motility assay), the old females cohoused with young flies exhibited a statistically significant result while males only trended in the same direction (3). The reasons behind these sex differences are a future area of study; stratified analysis should also be considered when utilizing other model systems for intergenerational housing.
Another fascinating finding is that lifespan of young flies was negatively affected by housing with old flies when housed in equal or exceeding number of aged flies (3). This finding is interesting as intergenerational housing is generally viewed as a mutually beneficial experience. The pathways activated in young flies to reduce the lifespan should be investigated further.
Housing conditions should also be considered in these experiments. Fruit flies, and humans, do not normally live in contained spaces. Investigation of the proximity needed to promote beneficial effects of intergenerational cohousing would be useful in both flies and humans.
This research raises many questions relevant to research at the Caminero Lab. It is curious whether number of mice housed together would impact experiments. In particular, isolation of mice during experiments (e.g., separating male mice due to fighting) could impact results obtained. Furthermore, this paper highlights the importance of sex differences; sufficient statistical power for stratified analysis should be implemented in order to capture any sex differences in our models.
Cho et al. use the fruit fly to study a complex concept, the effects of social determinants on aging.3 Despite limitations in comparing flies and humans (e.g., psychological complexity, stressors such as socioeconomic status), the results of this study urge the need for more research on intergenerational housing. In the meantime, Cho et al. remind us to keep our elderly loved ones close for a potentially positive effect.
References
Crimmins EM. Social hallmarks of aging: Suggestions for geroscience research. Ageing Research Reviews. 2020 Nov;63:101136. doi:10.1016/j.arr.2020.101136
Suleman R, Bhatia F. Intergenerational housing as a model for improving older-adult health. BC Med J. 2021 May;63(4):171-173.
Cho L-C, Yu C-C, Kao C-F. Social perception of young adults prolongs the lifespan of aged Drosophila. npj Aging Mech Dis. 2021 Dec;7(1):21. doi:10.1038/s41514-021-00073-8
McMaster University Graduate Studies. Symbiosis: Students and Seniors Co-Housing Program [Internet]. McMaster University; [cited 2021 Oct 7]. Available from: https://gs.mcmaster.ca/current-students/resources/spices/current-initiatives-2019-20/symbiosis/
Li W, Wang Z, Syed S, Lyu C, Lincoln S, O’Neil J, et al. Chronic social isolation signals starvation and reduces sleep in Drosophila. Nature. 2021 Sep 9;597(7875):239–44. doi:10.1038/s41586-021-03837-0
Larsson MC, Domingos AI, Jones WD, Chiappe ME, Amrein H, Vosshall LB. Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction. Neuron. 2004 Sep;43(5):703–14. doi:10.1016/j.neuron.2004.08.019
Figure 1: Lifespan is measured when old flies are housed with young flies (3). Old wild type Drosophila melanogaster are 40 days old and housed with young, 1-day old flies until endpoint.3 Old odorant receptor gene (or83b) or gustatory-specific cation channel gene (ppk23) mutant flies are 60 days old as mutant flies have a longer lifespan in general (3). At 60 days old, mutant flies are housed with young, 1-day old flies until endpoint.3 Ratios of housing include 1:3 and 1:9 old to young flies (3). Lifespan of wild type Drosophila is extended when housed in an old to young ratio of 1:3 and extended even further when young fly density is increased to 1:9 in males only (3). Lifespan of or83b and ppk23 mutants are not extended when housed in an old to young ratio of 1:3, however, lifespan is extended when the young fly density increased to 1:9 (3). Olfactory and gustatory sensation appears to play role in sensing of young flies (3). Figure made using biorender.com.