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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 considering each phase separately. Therefore, the precise correlation of age at every point in their lifespan must be determined. 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 between mice age and human age, following our previous article, which explained the relation in ages of laboratory rats with humans in detail.
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Review article
Men and mice: Relating their ages
Sulagna Dutta
, Pallav Sengupta
Ex-guest Teacher, Department of Physiology, Post-graduation Section, Serampore College, University of Calcutta, Kolkata, West Bengal, India
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
Developmental biology
Human age
Laboratory mice
Mice age
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 specic age group, although current outcomes are based on mice of an approximate age. To ll
this gap between approximation and accuracy, this review article is the rst 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.
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
Conictofinterest............................................................... 0
Fundingsource................................................................ 0
References.................................................................. 0
1. Introduction
Most studies in the eld 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) xxxxxx
Corresponding author at: Department of Physiology, Vidyasagar College for Women,
University of Calcutta, Kolkata, India.
E-mail address: (P. Sengupta).
LFS-14535; No of Pages 5
0024-3205 2015 Elsevier Inc. All rights reserved.
Contents lists available at ScienceDirect
Life Sciences
journal homepage:
Please cite this article as: S. Dutta, P. Sengupta, Men and mice: Relating their ages, Life Sci (2015),
years) differ signicantly, 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 difcult 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 eld.
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. [711] 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 scientic purposes and (B) animals cited in biomedical research papers (19502010).
Table 1
Commonly used strains of laboratory mice and their research applications.
Wean to
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
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) xxxxxx
Please cite this article as: S. Dutta, P. Sengupta, Men and mice: Relating their ages, Life Sci (2015),
approximation of the age of the experimental animal. To relate the life
stages of humans and mice scientically, 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 [710]. 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 34 months, beyond
which the precision is not sufcient 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 ossic
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 1418
years, whereas that of the lower body (femur and tibia) is detected at
the age of 1825 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
eshed 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
rst 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 at 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 protoconeparacone and hypoconemetacone are
completed; and the anteroloph and anteroconule are considerably
TW age 6: M3 is concave; M1 shows connected protoconeparacone
and hypoconemetacone; and all cusps of M2 are reduced further.
3. Relation between mice age and human age
Currently, biomedical studies achieve the highest accuracyand spec-
icity 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 signicant effect of environmental factors on
longevity. Intercurrent infections, parasitismand ghting lead to unpre-
dictable deaths. Three specic non-genetic factors (mammary tumour
virus, breeding history and diet) affecting lifespan have been identied
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 signicance of genetic factors for lifespan.
Fig. 2. The approximate age of mice can be determined by their physical attributes during the rst 2 weeks of life.
3S. Dutta, P. Sengupta / Life Sciences xxx (2015) xxxxxx
Please cite this article as: S. Dutta, P. Sengupta, Men and mice: Relating their ages, Life Sci (2015),
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;
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 34 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]).
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
pituitarygonadal 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 cornication 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 rst observable signs of puberty
in females are oestrogen dependent: vaginal introitus and a cornied
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;
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 is biologically dened 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 812 weeks of age, with an average of 10 weeks (P70) [23].
Mice weigh about 12 g at birth, with adult male mice reaching2030 g
and adult female mice1835 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 (1015
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 36.538 °C Age at pairing (mating) 68 weeks (male)
Respiratory rate 80230 breaths/min Weight at pairing 2030 g (male)
Heart rate 310840 beats/min Age at pairing (mating) 68 weeks (female)
Daily water consumption 58 ml/100 g body weight Weight at pairing 1835 g (female)
Daily food consumption 57 g/100 g body weight Length of oestrous cycle 45 days
Litter size 210 Duration of oestrus 816 h
Birth weight 12 g Time of ovulation 8.5 h after onset of oestrus
Breeding duration 1015 months Menopause 1718 months
Male adult weight 2030 g Time of copulation Midpoint of previous dark cycle
Female adult weight 1835 g Time sperm is detected in vagina 1648 h
Lifespan 13 years Time of implantation Late day 3.5
Blood volume 1.52.5 ml Length of gestation 1821 days
4S. Dutta, P. Sengupta / Life Sciences xxx (2015) xxxxxx
Please cite this article as: S. Dutta, P. Sengupta, Men and mice: Relating their ages, Life Sci (2015),
18;615 450 ¼41:37 human days ¼1miceday;
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 dened 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
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 specic life stage of the mice
under their studies.
Conict of interest
The authors declare that there are no conicts of interest.
Funding source
[1] Report of European Union, TheStatistics on the Number of Animals Used for Exper-
imental and Other Scientic Purposes, 2010.
[2] L. Demeritus, Of mice and men, EMBO Rep. 6 (2005) 539544.
[3] L. Demeritus, Aging in mouse and human systems: a comparative study, Ann. N. Y.
Acad. Sci. 1067 (2006) 6682.
[4] A. Balmain, C. Harris, Carcinogenesis in mouse and human cells: parallels and para-
doxes, Carcinogenesis 21 (2000) 347371.
[5] European Commission workshop, Are mice relevant models for human disease? U.
K, London, 2010 110.
[6] P. Sengupta, The laboratory rat: relating its age with humans, Int. J. Prev. Med. 4
(2013) 624630.
[7] A.R. Hardy, R.J. Quy, L.W. Huson, Esti mation of age in the Norway rat (Rattus
norvegicus) from the weight of the eyelens, J. Appl. Ecol. 20 (1983) 97102.
[8] F.P. Rowe, A. Bradeld, R.J. Quy, T. Swinney, Relationship between eye lens weight
and age in the wild house mouse (Mus musculus), J. Appl. Ecol. 22 (1985) 5561.
[9] R.C. Augusteyn, Growth of eye lens: 1. Weight accumulation in multiple species,
Mol. Vis. 20 (2014) 410426.
[10] E.C. Birney, R. Jenness, D.D. Baird, Eye lensproteins as criteria ofage in cotton rats, J.
Wild Lif. Manag. 39 (1975) 718728.
[11] D.R. Lord, The lens as an indicator of age in cotton-tail rabbits, J. Wildl. Manag. 23
(1959) 358360.
[12] M. Friend, A review of research concerning eyelens weight asa criteria of age in an-
imals, New York Fish Game J. 14 (1967) 152165.
[13] S.H. Kilborn, G. Trudel, H. Uhthoff, Review of growth plate closure compared with
age at sexual matu rity and lifesp an in laboratory animals, Contemp. Top. Lab.
Anim. Sci. 41 (2002) 2126.
[14] L.A. Kohn, P. Olson, J.M. Cheverud, Age of epiphyseal closure in tamarins and mar-
mosets, Am. J. Primatol. 41 (1997) 129139.
[15] C. Chou, P. Lee, K. Lu, H. Yu, A population study of house mice (Mus musculus
castaneus) inhabiting rice granaries in Taiwan, Zool. Stud. 37 (1998) 201212.
[16] J.E. Wilkinson, L. Burmeister, S.V. Brooks, C.C. Chen, S. Friedline, D.E. Harrison, J.F.
Hejtmancik, N. Nadon, R. Strong, L.K. Wood, M.A. Woodward, R.A. Miller, Rapamycin
slows aging in mice, Aging Cell 11 (2012) 675682.
[17] P. Sengupta, A small-scale cross-sectional study for the assessment of cardiorespira-
tory tness in relation to body composition and morphometric characters in sher-
men of Araku valley, Andhra Pradesh, India, Int. J. Prev. Med. 5 (2014) 557562.
[18] D.J. Fagundes, M.O. Taha, Animal disease model: choicescriteria and current animals
specimens, Acta Cir. Bras. 19 (2004) 5965.
[19] M. Hetherington, B. Doe, D. Hay, Mouse care and husbandry, in: I.J. Jackson, C.M.
Abbott (Eds.), Mouse Genetics and Transgenics: A Practical Approach, Oxford Uni-
versity Press, 2000.
[20] O. Pinter, Z. Beda, Z.Csaba, I. Gerendai, Differencesin onset of puberty in selected in-
bred mouse strains, Endocr. Abstr. 14 (2007) P617.
[21] J. Kercmar, S. Tobet, G. Majdic, Social isolation during puberty affects female sexual
behavior in mice, Front. Behav. Neurosci. 8 (2014) 337.
[22] M.H. Hagenauer, J.I. Perryman, T.M. Lee, M.A. Carskadon, Adolescent changes in the
homeostatic and circadian regulation of sleep, Dev. Neurosci. 31 (2009) 276284.
[23] R.A. Taft, M. Davisson, M.V. Wiles, Know thy mo use, Trends Gene t. 22 (2006)
[24] J.C. Grant, The upper limb, in: J.C. Grant (Ed.), Grant's Atlas of Anatomy, Baltimore:
Williams & Wilkins 1972, p. 100.
[25] K. Flurkey, J.M. Currer, D.E. Harrison, Themouse in aging research, in: J.G. Fox, et al.,
(Eds.), The Mouse in Biomedical Research, 2nd EditionAmerican College Laboratory
Animal Medicine (Elsevier), Burlington, MA 2007, pp. 637672.
[26] T. Bhattrai, K. Bhattacharya, P. Chaudhuri, P. Sengupta, Correlation of common
biochemical markers for bone turnover, serum calcium and alkaline phosphatase,
in post-menopausal women, Malays. J. Med. Sci. 21 (2014) 5861.
[27] T. Bhattarai, P. Chaudhuri, K. Bhattacharya, K, P. Sengupta, Effect of progesterone
supplementation on post-coital unilaterally ovariectomized superovulated mice in
relation to implantation and pregnancy, Asian J. Pharm. Clin. Res. 7 (2014) 2931.
5S. Dutta, P. Sengupta / Life Sciences xxx (2015) xxxxxx
Please cite this article as: S. Dutta, P. Sengupta, Men and mice: Relating their ages, Life Sci (2015),
... Reproductive cycles in middle-aged perimenopausal mice were analyzed after multiple-introductions of hESC-MPCs to evaluate the potential therapeutic function of these cells in reproductive aging. The cell introduction experiment was started in naturally aged mice at 10 months (44-weeks), which have ovarian function similar to that in human perimenopause (33). The evaluation of reproductive aging was tested in mice at 14 months (60-weeks), which have ovarian function similar to that in human menopause ( Fig. 1A and Fig. 2A). ...
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Objectives: There is no approved therapy to preserve ovarian health with aging. To solve this problem, we developed a long-term treatment of human embryonic stem cell-derived mesenchymal progenitor cells (hESC-MPCs) and investigated whether the cells retained the ability to resist ovarian aging, leading to delayed reproductive senescence. Materials and Methods: In a middle-aged female model undergoing natural aging, we analyzed whether hESC-MPCs have a beneficial effect on the long-term maintenance of reproductive fecundity and the ovarian reservoir or how their transplantation regulates ovarian function. Results: The number of primordial follicles and mice with regular estrous cycles were increased in perimenopausal mice underwent multiple introductions of hESC-MPCs compared to age-matched controls. The level of estradiol in the hESC-MPC group was similar to that of the young and adult groups. Embryonic development and live birth rate were increased in the hESC-MPC group compared with the control group, suggesting a delay in ovarian senescence by hESC-MPCs. In addition to the direct effects on the ovary, multiple-treatments with hESC-MPCs reduced ovarian fibrosis by downregulating inflammation and fibrosis-related genes via suppression of myeloid-derived suppressor cells (MDSCs) produced in bone marrow. Conclusions: Multiple introduction of hESC-MPCs could be a useful approach to maintain ovarian function in female reproductive aging and that these cells are promising sources for cell therapy to postpone the ovarian aging and retain fecundity in perimenopausal women.
... The current study deals with the neurological effects at younger ages and looks for the early changes manifested. Furthermore, the duration was also limited to account for the variation in the age and lifespan between mice and humans (Dutta and Sengupta 2016). After the completion of treatment, the animals were subjected to behavioural assays for 5 days, followed by euthanization by cervical dislocation and tissue collection for histological, biochemical, and molecular analysis. ...
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... According to Dutta et al's estimation (91) and the guideline of the Jackson lab ( research-labs/the-harrison-lab/gerontology/life-span-as-abiomarker), the transplanted mice at the experimental endpoint are approximately equivalent to the 20-year-old adolescents. ...
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Introduction Adenoid hypertrophy (AH) is a common upper respiratory disorder in children. Disturbances of gut microbiota have been implicated in AH. However, the interplay of alteration of gut microbiome and enlarged adenoids remains elusive. Methods 119 AH children and 100 healthy controls were recruited, and microbiome profiling of fecal samples in participants was performed using 16S rRNA gene sequencing. Fecal microbiome transplantation (FMT) was conducted to verify the effects of gut microbiota on immune response in mice. Results In AH individuals, only a slight decrease of diversity in bacterial community was found, while significant changes of microbial composition were observed between these two groups. Compared with HCs, decreased abundances of Akkermansia , Oscillospiraceae and Eubacterium coprostanoligenes genera and increased abundances of Bacteroides , Faecalibacterium , Ruminococcus gnavus genera were revealed in AH patients. The abundance of Bacteroides remained stable with age in AH children. Notably, a microbial marker panel of 8 OTUs were identified, which discriminated AH from HC individuals with an area under the curve (AUC) of 0.9851 in the discovery set, and verified in the geographically different validation set, achieving an AUC of 0.9782. Furthermore, transfer of mice with fecal microbiota from AH patients dramatically reduced the proportion of Treg subsets within peripheral blood and nasal-associated lymphoid tissue (NALT) and promoted the expansion of Th2 cells in NALT. Conclusion These findings highlight the effect of the altered gut microbiota in the AH pathogenesis.
... Finally, we extracted data for mice that can be considered "old" (>10 months) [40] from datasets that contained sufficient samples (at least nine animals per group). Mice within groups had a mean age of 12.35 months to 13.32 months and did not differ significantly in age (p = 0.249; example for Bacteroidetes/Firmicutes ratio analysis). ...
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The ageing of an organism is associated with certain features of functional decline that can be assessed at the cellular level (e.g., reduced telomere length, loss of proteostasis, etc.), but also at the organismic level. Frailty is an independent syndrome that involves increased multidimensional age-related deficits, heightens vulnerability to stressors, and involves physical deficits in mainly the locomotor/muscular capacity, but also in physical appearance and cognition. For sporadic Alzheimer’s disease, age per se is one of the most relevant risk factors, but frailty has also been associated with this disease. Therefore, we aimed to answer the two following questions within a cross-sectional study: (1) do Alzheimer’s model mice show increased frailty, and (2) what changes of the microbiota occur concerning chronological age or frailty? Indeed, aged 5xFAD mice showed increased frailty compared to wild type littermates. In addition, 5xFAD mice had significantly lower quantities of Bacteroides spp. when only considering frailty, and lower levels of Bacteroidetes in terms of both frailty and chronological age compared to their wild type littermates. Thus, the quality of ageing—as assessed by frailty measures—should be taken into account to unravel potential changes in the gut microbial community in Alzheimer’s disease.
Background Irritability, defined as proneness to anger, can reach a pathological extent. It is a defining symptom of disruptive mood dysregulation disorder and one of the most common reasons youths present for psychiatric evaluation and care. Aberrant responses to frustrative nonreward (FNR), the response to omission of expected reward, are central to the pathophysiology of irritability. FNR is a translational construct to study irritability across species. The development of preclinical FNR models would advance mechanistic studies of the important and relatively understudied clinical phenomenon of irritability. Methods We used FNR as a conceptual framework to develop a novel mouse behavioral paradigm named alternate poking reward omission. Juvenile mice were exposed to alternate poking reward omission and then examined with a battery of behavioral tests to determine the behavioral effect of FNR. Results FNR increased locomotion and aggression regardless of sex. These behavioral changes elicited by FNR resemble the symptoms observed in youth with severe irritability. FNR had no effect on anxiety-like, depression-like, or nonaggressive social behaviors. Conclusions Our alternate poking reward omission paradigm effectively elevated aggression and locomotion in juvenile mice. These frustration effects are directly related to behavioral symptoms of youth with severe irritability. Our novel behavioral paradigm lays the groundwork for further mechanistic studies of frustration and irritability in rodents.
Musculoskeletal disorders contribute substantially to worldwide disability. Anterior cruciate ligament (ACL) tears result in unresolved muscle weakness and posttraumatic osteoarthritis (PTOA). Growth differentiation factor 8 (GDF8) has been implicated in the pathogenesis of musculoskeletal degeneration following ACL injury. We investigated GDF8 levels in ACL-injured human skeletal muscle and serum and tested a humanized monoclonal GDF8 antibody against a placebo in a mouse model of PTOA (surgically induced ACL tear). In patients, muscle GDF8 was predictive of atrophy, weakness, and periarticular bone loss 6 months following surgical ACL reconstruction. In mice, GDF8 antibody administration substantially mitigated muscle atrophy, weakness, and fibrosis. GDF8 antibody treatment rescued the skeletal muscle and articular cartilage transcriptomic response to ACL injury and attenuated PTOA severity and deficits in periarticular bone microarchitecture. Furthermore, GDF8 genetic deletion neutralized musculoskeletal deficits in response to ACL injury. Our findings support an opportunity for rapid targeting of GDF8 to enhance functional musculoskeletal recovery and mitigate the severity of PTOA after injury.
Caloric restriction (CR) induces weight loss, but is associated with rapid weight regain upon return to ad libitum feeding. Our aim was to investigate effects of the macronutrient composition of the diet on weight loss and regain in elderly mice. Males, 18 months old, of the C57BL/6J strain were subjected to 4-week 30% CR followed by 4 weeks of ad libitum refeeding on either high-carb (HC), high-fat (HF) or high-protein (HP) diets (n = 22 each). Mice (n = 11) fed a chow diet ad libitum served as a control group (CON). Body mass and food intake were monitored daily. Twenty-four-hour indirect calorimetry was used to assess energy expenditure and substrate oxidation. Muscle and fat mass were evaluated with dissection of the tissues. Serum leptin and ghrelin levels were also measured. CR-induced weight loss did not differ between the diets. Weight regain was particularly fast for HF as mice overshot their initial weight by 12.8 ± 5.7% after 4-week refeeding when HC and HP mice reached the weight of the CON group. Weight regain strongly correlated with energy intake across the groups. The respiratory exchange ratio was lower in HF mice (0.81 ± 0.03) compared to HC (0.94 ± 0.06, p < 0.001), HP (0.89 ± 0.04, p < 0.001) and CON mice (0.91 ± 0.06, p < 0.01) during the refeeding. Serum leptin levels were higher in HF mice (1.03 ± 0.50 ng/mL) compared to HC (0.46 ± 0.14, p < 0.001), HP (0.63 ± 0.28, p < 0.05) or CON mice (0.41 ± 0.14, p < 0.001). Thus, CR induces similar weight loss in aging mice irrespective of the diet’s macronutrient composition. An HF diet leads to excessive energy intake and pronounced gain in body fat in spite of increased fat oxidation and serum leptin during the refeeding after CR.
The process of aging refers to physiological changes that occur to an organism as time progresses and involves changes to DNA, proteins, metabolism, cells, and organs. Like the rest of the cells in the body, gametes age, and it is well established that there is a decline in reproductive capabilities in females and males with aging. One of the major pathways known to be involved in aging is epigenetic changes. The epigenome is the multitude of chemical modifications performed on DNA and chromatin that affect the ability of chromatin to be transcribed. In this review, we explore the effects of aging on female and male gametes with a focus on the epigenetic changes that occur in gametes throughout aging. Quality decline in oocytes occurs at a relatively early age. Epigenetic changes constitute an important part of oocyte aging. DNA methylation is reduced with age, along with reduced expression of DNA methyltransferases (DNMTs). Histone deacetylases (HDAC) expression is also reduced, and a loss of heterochromatin marks occurs with age. As a consequence of heterochromatin loss, retrotransposon expression is elevated, and aged oocytes suffer from DNA damage. In sperm, aging affects sperm number, motility and fecundity, and epigenetic changes may constitute a part of this process. 5 methyl‐cytosine (5mC) methylation is elevated in sperm from aged men, but methylation on Long interspersed nuclear elements (LINE) elements is reduced. Di and trimethylation of histone 3 lysine 9 (H3K9me2/3) is reduced in sperm from aged men and trimethylation of histone 3 lysine 27 (H3K27me3) is elevated. The protamine makeup of sperm from aged men is also changed, with reduced protamine expression and a misbalanced ratio between protamine proteins protamine P1 and protamine P2. The study of epigenetic reproductive aging is recently gaining interest. The current status of the field suggests that many aspects of gamete epigenetic aging are still open for investigation. The clinical applications of these investigations have far‐reaching consequences for fertility and sociological human behavior.
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Unilateral ovariectomy (ULO) and its consequences with endocrine replacement in pregnant mice are important to examine both follicular dynamics as well as the outcome of implantation and pregnancy. In mice, ovariectomy on fourth day morning (D4), before pre-implantation estrogen secretion induces delayed implantation and embryonic diapauses, i.e. a state of suspended animation of embryos. The present study has beenundertaken to evaluate the effect of progesterone supplementation on rate of implantation in unilaterally ovariectomized superovulated mice. Our study reveals that progesterone (P4) may help to protect the loss of embryo before and after the implantation if ULO is done during pre-implantation period (D4).The present study also shows if ovary is present in one side of the animal, it secretes estrogen (E2) in circulation which acts systematically on the uterus rather than locally. The findings of the present study show that progesterone may help to avoid the loss of embryo before and after the implantation, if ULO is done during pre-implantation period (D4) and the serum estrogen (E2) acts systematically on the uterus. Thus, it can be concluded that implantation in the uterine horn where ovary is not there.
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By late 18th or early 19th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association. Thus, the current review attempts to compare rat and human age at different phases of their life. The overall findings indicate that rats grow rapidly during their childhood and become sexually mature at about the sixth week, but attain social maturity 5-6 months later. In adulthood, every day of the animal is approximately equivalent to 34.8 human days (i.e., one rat month is comparable to three human years). Numerous researchers performed experimental investigations in albino rats and estimated, in general, while considering their entire life span, that a human month resembles every-day life of a laboratory rat. These differences signify the variations in their anatomy, physiology and developmental processes, which must be taken into consideration while analyzing the results or selecting the dose of any research in rats when age is a crucial factor.
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Exposure to stress during puberty can lead to long-term behavioral alterations in adult rodents coincident with sex steroid hormone-dependent brain remodeling and reorganization. Social isolation is a stress for social animals like mice, but little is known about the effects of such stress during adolescence on later reproductive behaviors. The present study examined sexual behavior of ovariectomized, estradiol and progesterone primed female mice that were individually housed from 25 days of age until testing at approximately 95 days, or individually housed from day 25 until day 60 (during puberty), followed by housing in social groups. Mice in these isolated groups were compared to females that were group housed throughout the experiment. Receptive sexual behaviors of females and behaviors of stimulus males were recorded. Females housed in social groups displayed greater levels of receptive behaviors in comparison to both socially isolated groups. Namely, social females had higher lordosis quotients (LQs) and more often displayed stronger lordosis postures in comparison to isolated females. No differences between female groups were observed in stimulus male sexual behavior suggesting that female "attractiveness" was not affected by their social isolation. Females housed in social groups had fewer cells containing immunoreactive estrogen receptor (ER) α in the anteroventral periventricular nucleus (AVPV) and in the ventromedial nucleus of the hypothalamus (VMH) than both isolated groups. These results suggest that isolation during adolescence affects female sexual behavior and re-socialization for 1 month in adulthood is insufficient to rescue lordosis behavior from the effects of social isolation during the pubertal period.
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Background: The people residing in coastal areas of Visakhapatnam are mostly engaged in fishery, which is always been a physically demanding job, and numerous factors have direct or indirect impact on the health of fishermen; but, the data about their physical fitness or health status is quite scanty. Thus, the present study was conducted to assess their cardiorespiratory fitness pattern, as well as morphometric characters, which may be influenced by their occupation. Methods: In this retrospective cohort study, 25 young fishermen (mean age of 22.8 ± 1.92 years) were randomly selected from Araku valley of Visakhapatnam District, Andhra Pradesh and compared with 25 subjects who were randomly selected from college students (mean age of 21.9 ± 2.25 years) of Kolkata, West Bengal. Some physical and physiological fitness variables including height, weight, body mass index, body surface area, physical fitness index, anaerobic power, and energy expenditure were measured along with their morphometric characters. Results: Analysis of data indicated a significant difference in blood pressure, physical fitness index, energy expenditure, body fat percent and anaerobic power among fishermen compared to controls. However, there were no changes in morphometric characters between the two groups. Conclusions: Findings of this small-scale population-based study indicated that health and physical fitness of young fishermen is under the influence of both occupational workload and nutritional status, as found by body composition and morphometric characters.
Changes in body weight, lens weight, and the soluble and insoluble protein fractions of the eye lenses of a laboratory population of cotton rats (Sigmodon hispidus) were measured from 10 to 600 days of age. Body weight was found to be a reliable criterion for age determination for only the first 70 days. Soluble protein increased for about 120 days, but never was the most reliable indicator of age. Lens weight and insoluble lens protein were roughly equal as age indicators for the first 130 days, then insoluble protein became the best criterion as determined by narrowness of individual prediction limits calculated by regression techniques. It was concluded that any increase in accuracy of age estimation provided by the measure of insoluble lens protein should be evaluated carefully relative to the effort, time, and expense required by the technique. The relationship between apparent tyrosine and nitrogen in the soluble and insoluble protein fractions was investigated for young and old animals. The ratio was greater than 2:1 in all cases and differed in the soluble fraction between young and old animals and between the two fractions for younger animals. Decrease in the specific growth rates of the 4 parameters was similar for the first 100-150 days, then became negative for body weight and soluble protein but remained positive for lens weight and insoluble protein through 600 days of age.
(1) Eye lens growth curves were obtained from 200 male and 208 female laboratory-reared wild house mice (Mus musculus L.) between 3 and 72 weeks of age. (2) The relationship between age and dried lens weight was derived by regression analysis. The equations fitted to data for males and females respectively were log10 (age + 20 days) = 1.019 + 0.175 (paired lens weight) and log10 (age + 20 days) = 1.004 + 0.182 (paired lens weight); the correlation coefficients of the relationships were 0.97 and 0.96 respectively. (3) Lens weights were also measured in 170 male and 194 female farm-living mice whose ages were accurately known. Lens weight-age relationships were comparable in captive and wild-caught animals. (4) The accuracy of the lens method in determining age was examined by comparison of known and predicted ages. Infant, juvenile and three age-classes of adult animals were reliably separated by lens weight. The technique thus appears to be useful in the analysis of population structure in wild house mice.
(1) F1 litters from wild-caught Rattus norvegicus were maintained on surplus food and water in laboratory cages. (2) A relationship between age and dried lens weight was derived by regression analysis of data from ninety-six male and 105 female rats sacrificed at various known ages up to 18 months from birth. (3) A single predictive equation (combining males and females) is recommended for practical use which relates eylens weight to a transformed measure of age. The equation is log10 (age + 22 days) = 1·313 + 0·021 (paired lens weight) where 22 days is the gestation period and the correlation coefficient is 0.96.