Herbal supplement extends life span under some environmental conditions and boosts stress resistance

Abstract

Genetic studies indicate that aging is modulated by a great number of genetic pathways. We have used Drosophila longevity and stress assays to test a multipath intervention strategy. To carry out this strategy, we supplemented the flies with herbal extracts (SC100) that are predicted to modulate the expression of many genes involved in aging and stress resistance, such as mTOR, NOS, NF-KappaB, and VEGF. When flies were housed in large cages with SC100 added, daily mortality rates of both male and female flies were greatly diminished in mid to late life. Surprisingly, SC100 also stabilized midlife mortality rate increases so as to extend the maximum life span substantially beyond the limits previously reported for D. melanogaster. Under these conditions, SC100 also promoted robust resistance to partial starvation stress and to heat stress. Fertility was the same initially in both treated and control flies, but it became significantly higher in treated flies at older ages as the fertility of control flies declined. Mean and maximum life spans of flies in vials at the same test site were also extended by SC100, but the life spans were short in absolute terms. In contrast, at an independent test site where stress was minimized, the flies exhibited much longer mean life spans, but the survival curves became highly rectangular and the effects of SC100 on both mean and maximum life spans declined greatly or were abolished. The data indicate that SC100 is a novel herbal mix with striking effects on enhancing Drosophila stress resistance and life span in some environments, while minimizing mid to late life mortality rates. They also show that the environment and other factors can have transformative effects on both the length and distribution of survivorship, and on the ability of SC100 to extend the life span.

Conflict of interest statement

Competing Interests: The authors have the following interests. This study was funded in part by Genescient Corporation. The authors recommended and received approval for publication from the Genescient Board of Directors. Gregory Benford is on the Board. B. Villeponteau received personal income for consulting, and has been granted stock options from Genescient Corporation; he is also an inventor on a patent filing which Genescient has licensed (Pending Patent #14521877). K. Matsagas received compensation from, and has equity in, Genescient Corporation. C. Rizza has equity in Genescient Corporation; she is also an inventor on a patent filing which Genescient has licensed (Pending Patent #14521877). M. Horwitz has equity in Genescient Corporation. G. Benford has equity in Genescient Corporation and serves on the Board of Directors of Genescient Corporation. L.D. Mueller received personal income for consulting from, and has equity in Genescient Corporation. A. Nobles and R. Mockett have no competing interests. The SC100 formulation described herein provides the essential herbal components for several nutritional supplements (e.g. Stem Cell 100) that are currently commercially available and may eventually provide financial benefits to Genescient and its employees and shareholders. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Fig 1. Life span of Drosophila in cages with or without SC100 treatment.

Nine independent cages were used in 9 simultaneous longevity assays, with each cage having 250 male and 250 female B4 flies at 25°C. Female or male sets of 3 cages each (Cages A, B, or C) are shown with the Survivorship (percent survival) on the Y axis and the Adult Age in days on the X axis. These data show Survivorship for: C) Control Untreated flies (green triangles), T) SC100 Treated flies (blue open squares), and CT) Control/Treated flies that were switched to SC100 treatment on day 36 of the assay (red diamonds). For each treatment, females in Fig 1A, 1B, and 1C were housed together with males in Fig 1D, 1E, and 1F, respectively.

Fig 2. Male and female mortality rate changes in cages with or without SC100 treatment.

(A) These data are from the same longevity assays shown in Fig 1, wherein nine independent cages were used, with each cage having 250 males and 250 female B4 flies. To correlate mortality rates with the longevity assays, the male longevity data in the 3 sets of cages of Fig 1D, 1E, and 1F were pooled and composite average values were taken on each day for: C) Control untreated male flies (green triangles), T) SC100 treated male flies (blue squares), and CT) Control/Treated flies that were switched to SC100 treatment on day 36 of the assay (red diamonds). (B) and (C) show composite daily mortality rates for male flies (B) and female flies (C), which were determined by averaging the daily mortality rates from the three sets of cages for each treatment or control.

Fig 3. Life span of male and female Drosophila in single sex or combined sex vials with or without SC100 treatment: CA site.

3A (Females) and 3B (Males) show the survivorship curves for female and male B4 flies, respectively, where 4 flies of the same sex or 2 flies of each sex were housed at 25°C in each test vial, with 100 flies for each sex in the control or SC100-treated samples. In (A), the data for females are shown: Control females were housed in separate vials from males (solid green circles) versus housing of females with males in combined vials (solid green triangles); SC100 treated female flies are housed separate from males (open blue circles) or combined with males (open blue triangles). In (B), the data for males are shown: Control males were housed in separate vials from females (solid green circles) versus housing of males with females in combined vials (solid green triangles); SC100 treated male flies were housed separate from females (open blue circles) or combined with females (open blue triangles).

Fig 4. Life span of female and male B4 Drosophila in single sex vials with or without SC treatment: AL site.

Flies were separated by sex 1 d after eclosion, housed in groups of 25/vial at 25°C on a 12 h light: 12 h dark cycle, and supplemented with SC100 at doses of 0× (solid green triangles), 1/3× (solid blue squares), 1× (open black squares), and 3× (solid red squares) beginning 2 d after collection. Results are presented separately for females (A,B) and males (C,D) on banana medium (BM; A,C) and cornmeal (CM; B,D). For each medium and dosage, n = 3–4 vials (72–98 surviving flies) for females and 4 vials (89–100 survivors) for males. Results presented in Figs 4–6 were obtained concurrently.

Fig 5. Life span of female and male w 1118 Drosophila in single sex vials with or without SC treatment: AL site.

Flies were separated by sex 1 d after eclosion, housed in groups of 25/vial at 25°C on a 12 h light: 12 h dark cycle, and supplemented with SC100 at doses of 0× (solid green triangles), 1/3× (solid blue squares), 1× (open black squares), and 3× (solid red squares) beginning 2 d after collection. Results are presented separately for females (A,B) and males (C,D) on banana medium (BM; A,C) and cornmeal (CM; B,D). For each medium and dosage, n = 4 vials (96–102 surviving flies for females and 95–100 for males). Results presented in Figs 4–6 were obtained concurrently.

Fig 6. Life span of female and male y w Drosophila in single sex vials with or without SC treatment: AL site.

Flies were separated by sex 1 d after eclosion, housed in groups of 25/vial at 25°C on a 12 h light: 12 h dark cycle, and supplemented with SC100 at doses of 0× (solid green triangles), 1/3× (solid blue squares), 1× (open black squares), and 3× (solid red squares) beginning 2 d after collection. Results are presented separately for females (A,B) and males (C,D) on banana medium (BM; A,C) and cornmeal (CM; B,D). For each medium and dosage, n = 3–4 vials (75–102 surviving flies) for females and n = 4 vials (91–99 survivors) for males, except n = 2 vials (46 survivors) for females on 1/3× BM (A). Results presented in Figs 4–6 were obtained concurrently.

Fig 7. Survival curves for female and male B4 and O Drosophila in cages during heat and partial starvation treatment: CA site.

7A (Females) and 7B (Males) show the survivorship curves for B4 and O1 flies under heat (29°C) and partial starvation (10% dilution of normal food supply) stress. B4 Controls (solid green triangles) and stress-resistant O1 Control (solid red circles) flies were each housed in separate cages with both sexes combined (250 females and 250 males). Survivorship curves for the SC100 treated flies are shown for B4 treated (blue open squares) and for stress resistant O1 (open red diamonds) flies.