Social interaction-mediated lifespan extension of Drosophila Cu/Zn superoxide dismutase mutants

Abstract

Beneficial effects of social interaction on aging have been studied in humans and other species. We found that short-lived Drosophila mutants of the antioxidant enzyme Cu/Zn superoxide dismutase displayed a robust lifespan extension, with improved stress resistance and motor ability, upon cohousing with active flies of longer lifespan or younger age. Genetic, surgical, and environmental manipulations revealed motor and sensory components in behavioral interactions required for the lifespan extension induced by cohousing. Our results provide a definitive case of beneficial social interaction on lifespan and a useful entry point for analyzing the underlying molecular networks and physiological mechanisms.

Fig. 1.

Extension of lifespan, coupled with enhanced motor ability and stress resistance, of Sod flies by cohousing with helper flies. (A and B) Lifespan extension at 25 and 29°C. 4–10 Sod¹ flies (2–3 days old) were cohoused with w¹¹¹⁸ flies in each food vial. When cohoused with five helpers (filled circle), Sod¹ flies showed significant lifespan extension compared with control (open circle), P < 0.0001. This was true even for a single helper (B, filled triangle), P < 0.0001. Lifespan of w¹¹¹⁸ helper and wild-type CS at 25 and 29°C are shown for comparison in A and B. (C) Improved motor ability. Cohoused and control Sod¹ flies, both aged for 10 days at 25°C, were tested for climbing ability after mechanical agitation. As illustrated in the photographs (flies circled) and bar graphs (pooled from 10 trials), cohoused flies (Right, gray bars) climbed significantly higher than control (Left, open bars) 10 sec after the vials were tapped. (D) Enhanced stress resistance. Cohoused (gray bars) and control (open bars) Sod¹ flies aged at 25°C were challenged by mechanical stress of vortexing (left) on 3 consecutive days from the 10th day, or by 6-hr oxidative stress (paraquat feeding, Center) or heat stress (exposure to 38°C, Right) on the 9th day. Cohoused flies showed much higher survivorship compared with control. **, P < 0.01, paired t test. In this and the following figures, only male flies were used, with their numbers indicated in parentheses for each experiment.

Fig. 2.

Lifespan extension of Sod flies by younger short-lived helpers. (A) At 29°C, aged w helpers (beyond their median lifespan) failed to extend Sod¹ lifespan significantly (large open circle, P > 0.1). Corresponding data from Fig. 1B are shown for comparison (small filled circle, cohousing with 5 w helpers; small open circle, control). (B) At 25°C, young flies from short-lived Hk¹; qvr¹, and TrxR-1 stocks could serve as effective helpers. When cohoused with 5 Hk¹; qvr¹ helpers, Sod¹ flies showed significant lifespan extension (filled diamonds, P < 0.0001), comparable to the effect of cohousing with 5 w helpers (small filled circle, from Fig. 1A, P < 0.0001). TrxR-1 helpers, with even shorter lifespan than Hk¹; qvr¹, still conferred significant lifespan extension, albeit to a lesser extent (filed triangles, P < 0.001). (C) At 23°C, heteroallellic Sod³⁹/Sod⁶⁴ flies were extremely short-lived (open triangles) but showed significant lifespan extension (filled triangles, P < 0.01) when cohoused with young Sod¹ helpers. In the above experiments, dead or weakened helpers were replaced to maintain a constant number of 5 helpers per vial.

Fig. 3.

Physical presence and unimpaired motor ability of helpers were essential for lifespan extension of cohoused Sod flies. For comparisons, data for cohousing with w helpers (small filled circles) and control (small open circles) at 29°C from Fig. 1B are shown in A, B, and D and corresponding data at 25°C from Fig. 1A (small filled squares and small open squares) are shown in C. (A) At 29°C, exposing control Sod¹ flies to the food vial preconditioned by cohoused Sod-helper groups conferred no lifespan extension. Cohoused (filled squares) and control (open squares) groups were transferred daily to fresh food vials and kept for 12 hr. Afterward, the two groups were exchanged to expose to the food vials preconditioned by their counterparts for the remaining 12 hr of the day. (B) At 29°C, when cohoused with wing-clipped (wcd) helpers, Sod¹ flies (filled squares) showed significantly less lifespan extension (P < 0.001) compared with that conferred by intact helpers (small filled circles). (C) At 25°C, decapitated (dcp) helpers conferred only residual lifespan extension effect. They stood motionlessly and were not able to initiate interactions with Sod¹ flies (see text). Note, a residual lifespan extension (filled triangles, P < 0.01) occurred only after a prolonged latency (see text) compared with the cohousing effect with 5 w helpers and no helpers (small filled and open squares, from Fig. 1A). (D) At 29°C, the optimal lifespan extension requires the persistent presence of helpers. Transferring the helpers from cohoused groups to the control groups on the 5th day (vertical dotted line) caused a drop in survivorship of the deprived Sod¹ flies (filled triangles), only several days after losing helpers, demonstrating a latent beneficial effect. The initial Sod¹ control (open triangle) that received the transferred helpers on the 5th day still showed a decelerated mortality rate and significant lifespan extension (P < 0.001).

Fig. 4.

Roles of sensory-motor functions and activity levels in lifespan extension by cohousing. (A) At 25°C, constant darkness (DD) reduced the beneficial effect of helpers. Cohoused Sod¹ flies showed a reduced lifespan extension under DD (filled triangles, P < 0.001) compared with that under 12/12-hr light/dark (LD) cycles (small filled squares, from Fig. 1A). Lifespan of control groups under DD and LD conditions (open triangles vs. small open squares, from Fig. 1A) differed only slightly (although statistically significantly, P < 0.01). (B) At 29°C, sensory disruption in Sod¹ double-mutant flies para^OlfD/Y; Sod¹ (OlfD; Sod¹) and iav¹/Y, Sod¹ (iav; Sod¹). When cohoused with w helpers, OlfD; Sod¹ flies (filled triangles) defective in olfaction showed a reduction in lifespan extension. Lifespan extension was almost abolished in deaf iav; Sod¹ flies (filled squares), which might have additional mechanosensory and motor defects. Lifespan data for cohousing with w helpers (small filled circles) and control (small open circles) from Fig. 1B are shown for comparison. Control flies of double mutants OlfD; Sod¹ and iav; Sod¹ in the absence of helpers had a lifespan similar to that of Sod¹ flies (Table S4). (C) Enhanced locomotor activity of Sod¹ flies by cohousing with a young, but not aged, w helper. Histograms show distributions of activity counts per 10 min per food vial during a 2-day period (12/12 L/D cycle, 25°C). Young w helpers significantly increased Sod¹ fly activities (5 Sod¹ and 1 w per vial) and led to many bursts of high activity counts (Inset). Activity patterns of 6 Sod¹, single young w, or single aged w per vial are also shown (number of vials indicated).