Advantages and Limitations of Silkworm as an Invertebrate Model in Aging and Lifespan Research
Jiangbo Song1,2, Jianfei Zhang1,2 and Fangyin Dai1,2*
1State Key Laboratory of Silkworm Genome Biology, Southwest University, China
2 Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture, College of Biotechnology, Southwest University, China
Submission: June 02, 2018; Published: June 15, 2018
*Corresponding author:Fangyin Dai, State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, China.
How to cite this article: Jiangbo S, Jianfei Z, Fangyin D. Advantages and Limitations of Silkworm as an Invertebrate Model in Aging and Lifespan
Research . OAJ Gerontol & Geriatric Med. 2018; 4(4): 555641. DOI: 10.19080/OAJGGM.2018.04.555641
Aging and lifespan study had been the intense subjects of biological science. By now, nematode (Caenorhabditis elegans) and fruit fly (Drosophila melanogaster) are the most widely used experimental invertebrates in aging and lifespan researches. Considering the complicated mechanism, utilization of more model organisms is indispensable for its evolutionary conservation and species specificity. Moreover, it is easier to make a breakthrough in the experimental animal with low cost, relatively integrated and differentiated physiological systems, and simple body composition which is more susceptible to exogenous regulation than mammals. The silkworm, Bombyx mori, has been regarding as a new choice for some aging and lifespan research, especially in longevity genes’ function, signaling transduction and medicine efficacy evaluation study as its many features. Here, we discuss the objective conditions of this species as an invertebrate model for aging and lifespan research. Meanwhile, the major limitation reasons were also discussed for future work in research on aging and lifespan.
Keywords: Silkworm; Aging; Lifespan; Invertebrate Model
Animal model has become an indispensable tool in biology, medicine, pharmacy and other fields. However, the existing invertebrate experimental animals could not fully satisfy the needs for studying the complex mechanism of aging and lifespan regulation. Therefore, more experimental animal models need to be identified and developed . Meanwhile, the conservative lifespan regulation pathway in animal kingdom provides a natural basis for the study of the complex lifespan decision mechanism utilizing the lower animals . Silkworm (Bombyx mori) is one of the most important economic insects in agriculture and excellent experimental animals in classical genetics research . Simultaneously, silkworm possesses many characteristics which make it suitable for study the mechanism of aging and lifespan decision. Silkworm has been artificially bred for more than five thousand years, so some unique biological characteristics and cultural connotation have been formed .
With the overwhelming need for expanding new model organisms in the whole biological and medical research, the silkworm has been emerging as an organism of choice for research into the molecular regulation of aging and longevity . There are several laboratories and investigators exploring aging and lifespan using silkworm and our group is the first batch of
using this organism to address our questions of interest [6,5]. Although the studies in aging reporting advances in silkworm is significantly less than that in Caenorhabditis elegans, Drosophila melanogaster and Mus musculus, the silkworm is emerging as a novel invertebrate model in the aging and lifespan research field, which will further expand the choice scope of the invertebrate model alongside its more classical brethren: Caenorhabditis elegans and Drosophila melanogaster [7-9].
Silkworm has numerous advantages as a model organism for aging research, such as abundant mutant strains, clear genetic background, less ethical issues and low rearing cost, clear boundaries between different development stages, fasting model, and open blood circulation system, etc. There are numerous inherent beneficial traits in the use of silkworm to study aging, such as: the convenience of operation, the short growth and development cycle, the high propagation coefficient, and so on (Table 1). Major features and advantages are stated as following.
Some Trophic Facilitate Silkworm as an Invertebrate
Model for Aging and Lifespan Study: The silkworm possesses
a high reproductive rate, and the female moth can lay
approximately 500 eggs in several hours after mating, finally
these eggs will become the larva with the same developmental
status and genetic background, combine with the low cost
feature compared to mammalian model. This allows researchers
to obtain easily a large number of uniform individuals for aging
and lifespan investigations. Silkworms belong to oligotrophic
animals, which only feed on mulberry leaves. In recent decades,
researchers have developed a variety of silkworm artificial diets
which lead to silkworm feed and reproduce easily standardized
in the laboratory [10-13]. So that we can test the effect of drugs on
the lifespan of silkworms by daubing drugs on mulberry leaves
or adding drugs into artificial diets . The above characteristics
and standardized breeding of silkworm can ensure the reliability
and repeatability of experimental results which are not
disturbed by diet and culture conditions. The suitable individual
size of silkworm contributes to observation of morphology
and behavior, exogenous injection. In addition, due to the low
mobility of larva and the moth cannot fly, which is convenient for
breeding, management and lifespan measurement. Silkworms
are entirely dependent on human feeding and unable to survive
and reproduce in the wild environment. So it will not harm other
species and the local ecological environment even if it escapes
into the outside. Furthermore, silkworm is a non-emotional
animal so that there has less ethical issues in the study of aging
Strains and Physiology, Gene Regulation, and Functional
Genome Research Platform: The genetic resources available
in silkworm are rich, which have a clear genetic background.
The Silkworm Gene Bank at Southwest University in China
maintains most of these genetic systems, in particular, there are
a large number of genetic strains with tremendous differences
in lifespan. The genome sequence was completed previously
 and has been continually annotated providing an excellent
bioinformatics resource including genome sequence information
(Silk DB: http://www.silkdb.org) . The whole-genome
microarray was also constructed to analyze gene expression
(http://www.silkdb.org/microarray/). There is numerous online
resources information for silkworm strains (http://silkbase.
ab.a.u-tokyo.ac.jp/cgi-bin/index.cgi). Transgenic silkworms can
be easily generated by exogenous injection of DNA from micropyle
of newly laid eggs. RNAi and gene editing methodology has
advantage to study gene function in the genome for a variety of
different phenotypes. These platforms have aroused the concern
of silkworm researchers and become a forceful advantage in the
study of the silkworm aging and lifespan.
The Short Life Cycle and Relatively Obvious Boundaries
Between Different Development Stages: Silkworm possesses
a short life cycle with approximately 5-7 weeks in a generation
in standard feeding environment (25°C, approximately 75%
relative humidity with a 12L: 12D photoperiod). Maximum
lifespan is approximately 8 weeks. The whole life cycle of
silkworm undergoes larval, pupa, and adult stage. The adult
stage is equivalent to the aging stage of mammals. As the rapid
generation, it is easy to carry out research on intergenerational
aging and lifespan study. Compared with other more complicated
organisms, silkworm lifespan is easier to be influenced by
artificial manipulation, therefore, silkworm have a natural
material advantage as an invertebrate model to study how
external factor affect lifespan between intergeneration within a
short period. Meanwhile, the number of larval instars appears to
be firmly fixed at three in Drosophila melanogaster , while
the number of larval in star varies from four to six in silkworm.
This provides a better plasticity potential in lifespan study,
which could expand the display strength of altered lifespan.
Silkworm Adult Stage is a Natural Model for Studying
the Relationship of Fasting and Lifespan: Because silkworm
begins and completes mating and reproduction quickly at
the very early stage of the adult stage, so the adult stage is
generally considered to be the initial origination stage of silkworm organism aging. The eating and alimentary related
organs of adult silkworm are degraded and no feeding behavior
in silkworm adult stage. However, their energy is sufficient to
support mating, reproduction, and survival 1-2 weeks. So, it is a
natural invertebrate animal model for studying the relationship
between fasting and lifespan. Few species in nature have such
feature. This primary advantage of the model is it could exclude
factors such as food intake quantity and type from interfering
with the lifespan statistical results in aging and lifespan studies.
Meanwhile, this model provides great convenience for studying
energy metabolism and lifespan.
Silkworm Possess an Open Hemolymph Circulation
System: Silkworm has an open blood circulation system
without blood vessels, such a system can quickly transport and
transform all kinds of components and energy. At the same time,
it can initiate the immune prevention and secrete a variety of
proteins to effectively eliminate foreign pathogenic factors when
stimulated by foreign pathogenic microorganisms. Although the
open hemolymph system of silkworms is simpler in structure
than that of mammals, they have a similar pharmacokinetic
mechanisms of chemicals. This makes it possible for the
silkworm to be used as a rapid screening model for bioactive
natural components screening and drug efficacy evaluation.
Microinjection can directly delivery the drug into the hemolymph
of silkworm. Because of silkworm open hemolymph system
and simpler structure compare to multi-layer wall structure of
mammals, this structure reduces the loss of the drug as it passes
through the walls of blood vessel, which can make the drug more
quickly and efficiently spread to the whole body. Finally, the drug
can directly reach various organs and is absorbed to function.
Despite the numerous advantages, there are several
limitations in the use of silkworm as a model system for the
study of aging and lifespan (Table 2).
Long Divergence Time With Mammals in Evolution:
Silkworm is a poikilotherm animal and own a far evolutionarily
relationship with humans, being separated by hundreds of
millions of years. More dominating factor is the fact that many
important physiologically systems was absent in the silkworm,
especially the acquired immune system. Moreover, the most
intensely studied set of aging mutations in silkworm are those
also specifying voltinism and moultinism development and
there have little relevance between “voltinism and moultinism”
state with mammalian aging and lifespan.
Some Human Orthologous Genes is Absent on Aging
and Lifespan in Silkworm: The results of genome sequence
showed that there were 14623 genes in silkworm. Through
the identification of orthologous genes between silkworm and
human, it was found that 8469 genes in silkworm had direct
homologous genes in human . However, there are still 6154
genes in silkworms without corresponding human homologous
genes, accounting for 42% of the total genes of silkworms, which
may contain some genes that strongly associate with aging and
longevity. For example, sirtuin 1 is a gene involved in processes
such as calorie restriction (CR), chromatin remodeling, stress
response, and DNA repair, and there is no corresponding
orthologous gene in silkworm [18,19]. The effects of these
genes on aging and lifespan regulation cannot be carried out in
silkworm. Therefore, this has brought some limitations to the
exploration of silkworm as an invertebrate animal model for
aging and lifespan research.
With these advantages, silkworms is emerging as an
invertebrate model for the aging and lifespan mechanism study,
and could also serve as a novel replaceable laboratory animal
to provide early reference for mammalian and clinical screening
for lifespan extending drugs and pharmacodynamics evaluation.
The more expandable application using silkworm would also rise
in aging and lifespan field [20,21]. We hope that the advantages
of the silkworm as an invertebrate model for aging and lifespan
will be further exploited in the near future, and some limitations
could be overcome gradually with the continuously efforts of
the colleagues in the field. Studies using silkworm to unravel
molecular mechanisms behind aging and lifespan will provide
new insights into this field.
Aging and lifespan research in our lab has been supported
by the Hi-Tech Research and Development 863 Program of China
(grant No. 2013AA102507) over the years, and grants from the
Fundamental Research Funds for the Central Universities in
China (No. XDJK2016E017).