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Review article
Men and mice: Relating their ages
Sulagna Dutta
a
, Pallav Sengupta
b,
⁎
a
Ex-guest Teacher, Department of Physiology, Post-graduation Section, Serampore College, University of Calcutta, Kolkata, West Bengal, India
b
Department of Physiology, Vidyasagar College for Women, University of Calcutta, Kolkata, West Bengal, India
abstractarticle info
Article history:
Received 20 July 2015
Received in revised form 19 October 2015
Accepted 22 October 2015
Available online xxxx
Keywords:
Age
Developmental biology
Human age
Laboratory mice
Mice age
Physiology
Since the late 18th century, the murine model has been widely used in biomedical research (about 59% of total
animals used) as it is compact, cost-effective, and easily available, conserving almost 99% of human genes and
physiologically resembling humans. Despite the similarities, mice have a diminutive lifespan compared to
humans. In this study, we found that one human year is equivalent to nine mice days, although this is not the
case when comparing the lifespan of mice versus humans taking the entire life at the same time without consid-
ering each phase separately. Therefore, the precise correlation of age at every point in their lifespan must be de-
termined. Determining the age relation between mice and humans is necessary for setting up experimental
murine models more analogous in age to humans. Thus, more accuracy can be obtained in the research outcome
for humans of a specific age group, although current outcomes are based on mice of an approximate age. To fill
this gap between approximation and accuracy, this review article is the first to establish a precise relation be-
tween mice age and human age, following our previous article, which explained the relation in ages of laboratory
rats with humans in detail.
© 2015 Elsevier Inc. All rights reserved.
Contents
1. Introduction............................................................... 0
2. Agedeterminationoflaboratorymice:commonmethods........................................... 0
2.1. Weightofeyelens......................................................... 0
2.2. Musculoskeletalexamination:epiphysealclosure........................................... 0
2.3. Bodyweightassessment...................................................... 0
2.4. TWpattern............................................................ 0
3. Relationbetweenmiceageandhumanage................................................. 0
3.1. Relationbetweentheirlifespans................................................... 0
3.2. Weaningperiodofmiceandhuman................................................. 0
3.3. Miceandhumanagetoattainpuberty................................................ 0
3.4. Ageofadulthoodonsetinmiceanditsrelationtohumanageofadulthood............................... 0
3.5. Reproductivesenescenceinmiceandhumans ............................................ 0
3.6. Post-senescencephaseinmiceandhumans ............................................. 0
4. Conclusions............................................................... 0
Conflictofinterest............................................................... 0
Fundingsource................................................................ 0
References.................................................................. 0
1. Introduction
Most studies in the field of life science (almost 59% of the experi-
mental studies [1]) use experimental murine models (Mus musculus)
for investigating the implications on human health and body (Fig. 1).
In terms of their maximum lifespan, mice (4 years) and humans (120
Life Sciences xxx (2015) xxx–xxx
⁎Corresponding author at: Department of Physiology, Vidyasagar College for Women,
University of Calcutta, Kolkata, India.
E-mail address: pallav_cu@yahoo.com (P. Sengupta).
LFS-14535; No of Pages 5
http://dx.doi.org/10.1016/j.lfs.2015.10.025
0024-3205/© 2015 Elsevier Inc. All rights reserved.
Contents lists available at ScienceDirect
Life Sciences
journal homepage: www.elsevier.com/locate/lifescie
Please cite this article as: S. Dutta, P. Sengupta, Men and mice: Relating their ages, Life Sci (2015), http://dx.doi.org/10.1016/j.lfs.2015.10.025
years) differ significantly, although murine models have been widely
used to analyse human body functioning and its modulation (see Ref.
[2]). In two pioneering studies, Sir L. Demeritus (published in 2005
and 2006) documented their similarities and differences in diverse met-
abolic processes, describing the molecular process of ageing in detail
(see Refs. [2,3]), but not the precise correlation of their ages in different
phases of their lifespan.
Despite the large differences in their lifespan, humans and mice
show similarpatterns in disease pathogenesis as well as organ and sys-
temic physiology. Their cells contain similar molecular structures that
regulate the functioning of cells, differentiation. Moreover, the molecu-
lar mechanism of ageing in mice is similar to that in humans (see Ref.
[3]). For instance, mice acquire mutations in the spectrum of proto-
oncogenes and tumour suppressor genes, similar to those affected in
human cancers (see Ref. [4]). Almost 99% of mouse genes resemble
the human genome, thus making the murine model an ideal candidate
for studying the functions of human genes in health as well as in the reg-
ulation ofmultifactorialdiseases such as cancer, cardiovasculardiseases,
diabetes and arthritis (Table 1). Acute promyelocytic leukaemia (APL),
although previously untreatable, is currently treated in humans after
successful experimentation in murine models. Although certain larger
mammals can better simulate human genotypic and phenotypic fea-
tures, they can be expensive and difficult to maintain or handle [5].
Mice provide analogous experimental conditions and comparable
results to humans. Findings of general experiments with mice, pharma-
ceutical trials for newly designed drugs in murine models, or studieson
different developmental phases of mice are intended to be applied on
human health and life. In all such cases, using mice of an approximate
age rather than precisely correlated age or phase with humans limits
the accuracy of experiments and their implications for human physiol-
ogy. It is imperative that researchers consider the phase and age of ani-
mals used in experiments in relation to human physiology, which was
explained in detailin our previous review work on therelation between
the age of rats and humans (see Ref. [6]). Thus, the aim of this compre-
hensive review is to precisely analyse the relation between mice age
and human age in various life stages to bridge the gap between the ap-
proximation and accuracy of future research in the biomedical field.
2. Age determination of laboratory mice: common methods
Various methods havebeen used to correlate the ages of small mam-
mals with human age, for example, by determining the weight of eye
lens (see Refs. [7–11] and [12]), epiphyseal closure (see Refs. [13,14]),
tooth wear (TW) pattern [15], and body weight correlation [15].As
these methods provide a relative age that does not exactly coincide
with the exact age, more than one method is required for a closer
Fig. 1. (A) Use of animals in research and other scientific purposes and (B) animals cited in biomedical research papers (1950–2010).
Table 1
Commonly used strains of laboratory mice and their research applications.
Mostly
used
strains
Strain
abbreviation
Rotation
length
(weeks)
a
Mean
litter
size
Wean to
born
ratio
Research applications
BALB/C Cby 30 4.40 0.88 Mostly in immunological research
C3H/HEJ C3 22 4.60 0.90 In a wide variety of research including cancer, infectious disease, sensoneural and cardiova scular research
C57BL/6 J B6 30 4.90 0.80 General purpose, cardiovascular research, background strain for mice carrying transgenes, spontaneous or
targeted mutations
DBA/2 J D2 26 4.70 0.80 General purpose, atherosclerosis, glaucoma research.
SWR SW 22 4.6 0.80 General purpose, highly susceptible to experimental allergic encephalomyelitis
129P3/J 129P 26 5.0 0.90 Spontaneous testicular teratomas, targeted mutagenesis
NZB/B1NJ NZB 26 4.5 0.90 Autoimmunity
a
The average length of time a breeding unit reliably delivers progeny (also called the optimum reproductive lifespan).
2S. Dutta, P. Sengupta / Life Sciences xxx (2015) xxx–xxx
Please cite this article as: S. Dutta, P. Sengupta, Men and mice: Relating their ages, Life Sci (2015), http://dx.doi.org/10.1016/j.lfs.2015.10.025
approximation of the age of the experimental animal. To relate the life
stages of humans and mice scientifically, we used methods of age deter-
mination in mice by reviewing previous articles.
2.1. Weight of eye lens
Several studies have used the weight of the eye lens across mamma-
lian life stages as an indicator of the age correlation among different spe-
cies [7–10]. The increase in the weight of the eye lens follows an
asymptotic curve throughout the lifespan of most mammals [11].In
the late 1980s, this technique was considered a vital tool to correlate
the ages of different mammalianspecies at various lifestages. However,
it serves as an important indicator only up to 3–4 months, beyond
which the precision is not sufficient to determine the exact age of
small mammals (see Refs. [12]).
2.2. Musculoskeletal examination: epiphyseal closure
As dental developmentis minimal in foetal animals, their age can be
estimated based on bone formation such as long bone lengths, the de-
velopment of the ilium, and the petrous portion of the temporal bone.
Provided the measurements are accurate, formulae involving the corre-
lation between bone length and age can be usedto determine the corre-
spondingage of the animal. The bones of the upper and lower limbs and
hip joint are mostly used to analyse the age of the experimental animal.
In young animals, metopic suture closure and the emergence of ossific
centres are indicators of age. In addition, the growth of epiphyseal
plates, and closure of the same in some species, is an indicator of the
onset of sexual life in mammals, as observed in different mammalian
species (see Ref. [13]). In humans, closure of the epiphysis in the
bones of the upper body (namely, wrist, shoulder joint, humerus, ulna,
radius, metacarpals and phalanges) is observed at the age of 14–18
years, whereas that of the lower body (femur and tibia) is detected at
the age of 18–25 years. Bone remodelling and maintenance of bone in-
dicate early adulthood, whereas late adulthood is marked by observa-
tions of bone wear and tear. Epiphyseal evaluation requires detailed
examination of skeletal remains along with radiological assessment in
fleshed material [14].
2.3. Body weight assessment
In studies using laboratory animals of varying unknown ages, it is
important to differentiate the cohort groups according to their age. For
this purpose, the frequency distribution of their body weights can be
plotted to represent different cohorts. Then the statistical models in
the body weight distribution are determined, from which the different
age classes can be predicted [15]. The approximate age of mice pups
can also be determined by their physical characteristics during the
first 2 weeks of their life (Fig. 2).
2.4. TW pattern
As laboratory mice experience constant attrition of their molar teeth
when grinding food, the degree of TW is proportional to the age of the
mice [15]. The skulls of mice have been observed under a dissecting mi-
croscope for dental eruption and wear patterns of the upper molar
(M) (whichare used in determining the age classes). Based on theseob-
servations, a standardized age chart is formulated:
TW age 1: M3 is partly erupted and unworn.
TW age 2: M3 is completely erupted and slightly worn, whereas M1
and M2 show negligible wear on their occlusal surface.
TW age 3: M3 is visibly roughly worn with a concave occlusal sur-
face; M1 shows a protocone and paracone, and fused anterolingual
and anterolabial conules; and M2 shows a protocone and paracone,
as well as fused hypocone and metacone.
TW age 4: M3 becomes flat or concave; M1 shows a completely
worn occlusal surface; and M2 shows greatly decreased
anterolingual and anterolabial conules.
TW age 5: all cusps of M1 become more diminutive; the connections
between the M2 protocone–paracone and hypocone–metacone are
completed; and the anteroloph and anteroconule are considerably
reduced.
TW age 6: M3 is concave; M1 shows connected protoconeparacone
and hypocone–metacone; and all cusps of M2 are reduced further.
3. Relation between mice age and human age
Currently, biomedical studies achieve the highest accuracyand spec-
ificity due to the advances in technology. Therefore, in experiments
with mice representing humans, the mice age must be precisely deter-
mined in relation to human age, in terms of both the lifespan and indi-
vidual life stages. In the following section, we present human age in
relation to different developmental stages of mice.
3.1. Relation between their lifespans
Mice have a shorter and accelerated early life, compared with
humans. As the developmental stages of mice are not uniform com-
pared with humans, the correlation between their entire lifespans can-
not be used to determine human days in terms of mice days and vice
versa, at every life stage.
Studies on the broad distributions of age at death within inbred
strains and variances in the mean survival rate of mice under diverse
conditions revealed the significant effect of environmental factors on
longevity. Intercurrent infections, parasitismand fighting lead to unpre-
dictable deaths. Three specific non-genetic factors (mammary tumour
virus, breeding history and diet) affecting lifespan have been identified
in controlled investigations. Individual alterations in these factors may
result in differences in lifespan within a single colony of a particular
strain. Other perceptible within-strain life-history variables,such as sea-
son of birth, age of parents at birth, or lifespan of parents, have no dis-
cernable effect on mouse lifespan. Differences between strains have
also demonstrated the significance of genetic factors for lifespan.
Fig. 2. The approximate age of mice can be determined by their physical attributes during the first 2 weeks of life.
3S. Dutta, P. Sengupta / Life Sciences xxx (2015) xxx–xxx
Please cite this article as: S. Dutta, P. Sengupta, Men and mice: Relating their ages, Life Sci (2015), http://dx.doi.org/10.1016/j.lfs.2015.10.025
The average lifespan of laboratory mice is about 24 months [16]
(Table 2), whereas the life expectancy of humans globally is about 80
years, which varies among countries based on economic status [17].
Therefore, considering both lifespans, the correlation can be calcu-
lated as follows:
80 365ðÞ2365ðÞ¼40 human days ¼1miceday;
and
365 40 ¼9:125 mice days ¼1 human year:
Thus, one human year is almost equivalent to 9 mice days when cor-
relating their entire lifespan.
3.2. Weaning period of mice and human
Mammals are altruistic as they nurse and feed their young ones,
which later withdraw from mother's milk and learn independent feed-
ing habits and survival strategies in their environment. According to the
medical dictionary, ‘weaning is the transition of the human infant from
breast-feeding or bottle nursing and commencement of nourishment
with other food’(see Ref. [18]).
Mice are weaned at 3–4 weeks, approximately on 28th days (P28),
after birth. While weaned, the pups become robust, active, their eyes
open up, teeth and fur develop well and are able to jump, feed them-
selves and drink on their own [19]. On the other hand the average
weaning age for humans is about 6 months (180 days) (see Ref. [6]).
Thus,
180 28 ¼6:43 human days ¼1 mice day and 365 6:43
¼56:77 mice days ¼1 human year:
Therefore, in this developmental phase, one human year equals
56.77 mice days.
3.3. Mice and human age to attain puberty
Puberty is the peak phase of maturation of the hypothalamo–
pituitary–gonadal axis, which is characterized by alterations in gonado-
tropin levels in circulation and elevated levels of sex steroids. The most
common markers of puberty onset in mice are vaginal cornification and
onset of the oestrous cycle in females and balanopreputial separation
(BPS) in males [20]. At birth, the pituitary glands of mice are physiolog-
ically undifferentiated from gonadotropins. Moreover, the ovaries are
unresponsive to gonadotropin. Sex differentiation of the pituitary usu-
ally occurs by day 6 (P6) in males and before day 12 (~P12) in females.
Typically, sexual maturity coincides with rising titres of circulating go-
nadotropin after 4 weeks of age. The first observable signs of puberty
in females are oestrogen dependent: vaginal introitus and a cornified
vaginal smear. The vagina may open as early as day 24 (P24), and it is
often reported open by 4 weeks (~P28) of age. In addition, oestrus,
that is, the willingness to mate, does not always occur on schedule.
The average age at which mice attain puberty is about 42 days (P42)
[21,22], and the average age in humans is about 11.5 years
(11.5 × 365 = 4198 days) [23].
Thus, in the prepubertal phase,
4198 42 ¼99:95 human days ¼1miceday;
and
365 99:95 ¼3:65 mice days ¼1humanyear:
Thus, in this phase, one human year is equivalent to 3.65 mice days.
3.4. Age of adulthood onset in mice and its relation to human age of
adulthood
Adulthood is biologically defined as the age at which sexualmaturity
is attained in the case of mice or other animals, but it is associated with
several psychological and social concepts in humans. Mice attain sexual
maturity at 8–12 weeks of age, with an average of 10 weeks (P70) [23].
Mice weigh about 1–2 g at birth, with adult male mice reaching20–30 g
and adult female mice18–35 g [23]. In humans, growth plate closure is
used to differentiate between adolescence and adulthood, as growth
plates in the scapula fuse last, at about 20 years of age on average
(365 × 20 = 7300 days) [13,24].
Therefore, from these data, it can be calculated that
7300 70 ¼104:3 human days ¼1miceday;
which indicates that
365 104:3¼2:60 mice days ¼1humanyear:
Thus, during the adult phase, 2.60 mice days are equivalent to one
human year.
3.5. Reproductive senescence in mice and humans
Although senescent changes in mice begin in middle age (10–15
months), the biomarkers of ageing are not detected then. However, re-
productive functions cease at the end of middle age, and theupper limit
for the middle-aged group is considered to be 15 months (P450) of age
in mice [25]. In humans, menopause in women is a marker of reproduc-
tive senescence, which is associated with the termination of the fertility
cycle [26,27]. The average age ofmenopause in women,according to the
American Medical Association, is 51 years (51 × 365 = 18,615 days)
(see Ref. [6]).
Table 2
General physiology and reproductive data of laboratory mice.
Common physiological data Reproduction data
Body temperature 36.5–38 °C Age at pairing (mating) 6–8 weeks (male)
Respiratory rate 80–230 breaths/min Weight at pairing 20–30 g (male)
Heart rate 310–840 beats/min Age at pairing (mating) 6–8 weeks (female)
Daily water consumption 5–8 ml/100 g body weight Weight at pairing 18–35 g (female)
Daily food consumption 5–7 g/100 g body weight Length of oestrous cycle 4–5 days
Litter size 2–10 Duration of oestrus 8–16 h
Birth weight 1–2 g Time of ovulation 8.5 h after onset of oestrus
Breeding duration 10–15 months Menopause 17–18 months
Male adult weight 20–30 g Time of copulation Midpoint of previous dark cycle
Female adult weight 18–35 g Time sperm is detected in vagina 16–48 h
Lifespan 1–3 years Time of implantation Late day 3.5
Blood volume 1.5–2.5 ml Length of gestation 18–21 days
4S. Dutta, P. Sengupta / Life Sciences xxx (2015) xxx–xxx
Please cite this article as: S. Dutta, P. Sengupta, Men and mice: Relating their ages, Life Sci (2015), http://dx.doi.org/10.1016/j.lfs.2015.10.025
Thus,
18;615 450 ¼41:37 human days ¼1miceday;
and
365 41:37 ¼8:82 mice days ¼1humanyear:
Thus, during reproductive senescence, 8.82 mice days are equivalent
to one human year.
3.6. Post-senescence phase in mice and humans
In mice, senescence is defined by a minimum age of at least 18
months [25], when thebiomarkers of old age are prominently detected,
with a lifespan of around 24 months, as stated in the previous sections.
Thus, the post-senescence period in mice is about 2 months (60 days),
and female humans may survive approximately for 10,585 days after
senescence.
Thus,
10;585 60 ¼176:4humandays¼1miceday;
365 176:4¼2:069 mice days ¼1humanyear:
Thus, in thesenescence phase, 2.069 mice days are equivalent to one
human year.
4. Conclusions
This article reveals the wide variations in the developmental dura-
tions and phases of mice versus humans, although murine models are
essential in biomedical science to study human physiology and its mod-
ulations. The relative ages of mice differ depending on the life stage.
Therefore, it is imperative that researchers know the precise correlation
between mice age and human age at a specific life stage of the mice
under their studies.
Conflict of interest
The authors declare that there are no conflicts of interest.
Funding source
None.
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Please cite this article as: S. Dutta, P. Sengupta, Men and mice: Relating their ages, Life Sci (2015), http://dx.doi.org/10.1016/j.lfs.2015.10.025
