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JAVMA, Vol 246, No. 1, January 1, 2015 Vet Med Today: Reference Point 67
In the broadest sense, aging refers to the natural, pro-
gressive series of life stages beginning with concep-
tion and continuing through development, maturation,
and senescence. Most often, however, the term is more
narrowly used to refer to the complex set of biological
changes occurring in older individuals that result in a
progressive reduction of the ability to maintain homeo-
stasis when exposed to internal physiologic and exter-
nal environmental stresses.1 These changes ultimately
lead to decreased vitality, increased vulnerability to dis-
ease, and eventually death.
Older dogs make up a substantial proportion of
the pet dog population in the United States. One sur-
vey,2 for example, estimated that 30% to 40% of the 78
million pet dogs in the United States in 2007 were ≥
7 years old, and a more recent survey3 suggested that
the percentage of older dogs may be as high as 49%. Of
course, the rate at which individual dogs exhibit overt
signs of aging is affected by a number of factors, includ-
ing breed, adult body size, genetic makeup, exposure
to injuries and disease, and nutritional status. When all
breeds are considered together, the mean lifespan of do-
mestic dogs is approximately 13 years.4 However, body
size substantially affects lifespan in dogs.5–7 Thus, be-
cause of their shorter lifespans, giant- and large-breed
dogs (ie, dogs with a mature body weight ≥ 22.7 kg
[50 lb]) should probably be classified as senior when
they are 6 to 8 years of age and as geriatric when they
are ≥ 9 years of age. Medium- and small-breed dogs (ie,
dogs with a mature body weight < 22.7 kg) may be clas-
sified as senior when they are 7 to 10 years of age and as
geriatric when they are ≥ 11 years of age. Regardless of
Common physical and functional changes
associated with aging in dogs
the specific age cutoffs used, senior and geriatric dogs
can all be considered to be aged and to likely have at
least some changes associated with aging.
Some changes associated with aging can be consid-
ered favorable. For example, aged dogs often are well-
behaved and have well-established habits. Other aging
changes are neither positive nor negative, such as gray-
ing of the muzzle or a moderate reduction in activity
level. Less desirable changes are those associated with
illness, changes in mobility, or the development of be-
havioral problems. Collectively, deteriorative changes
that negatively affect an aged dog’s overall quality of life
are referred to as senescence.8
Several theories have been proposed to explain the
phenomena of aging and senescence.9 Many of these
focus on genetic controls, such as the somatic muta-
tion and gene regulation theories. Others examine the
impact of temporal changes on homeostatic mecha-
nisms of various body systems or the accumulation
of damaging products as a result of cellular aging. For
example, the oxidative stress theory postulates that ag-
ing is linked to energy expenditure and the cumulative
cellular damage caused by free radicals derived from
external sources as well as internal sources such as mi-
tochondrial respiration and immune cell reactions.10,11
However, none of these theories by itself explains all of
the changes that are observed during aging, and many
of the theories that have been advanced are not neces-
sarily mutually exclusive. A more cogent view is that
aging and senescence are multifaceted processes influ-
enced by genetics and a myriad of internal and external
environmental factors.
Naturally, many older dogs are cherished fam-
ily members whose owners are committed to provid-
ing them with the best of care. When examining older
dogs and when providing owners of older dogs advice
regarding their care, veterinarians should have an ap-
preciation of the types of changes that reflect typical
age-related changes (ie, healthy aging) versus an under-
Reference Point
ABBREVIATIONS
GAG Glycosaminoglycan
GI Gastrointestinal
HPA Hypothalamic-pituitary-adrenal
T4 Thyroxine
TSH Thyroid-stimulating hormone (thyrotropin)
From All Pets Dental, 17100 Royal Palm Blvd, Weston, FL 33326
(Bellows); Animal HealthQuest Solutions LLC and All Animal
Eye Care Inc, 300 Central Blvd, Jupiter, FL 33458 (Colitz);
P&G Pet Care, 8700 Mason-Montgomery Rd, Mason, OH
45040 (Daristotle, Lepine, Zhang); Nutritional Neuroscience
and Aging Laboratory, Pennington Biomedical Research Cen-
ter, Louisiana State University, Baton Rouge, LA 70808 (In-
gram); the Department of Medicine and Epidemiology, School
of Veterinary Medicine, University of California-Davis, Davis,
CA 95616 (Marks); the Department of Physiology and Pharma-
cology, College of Veterinary Medicine, University of Georgia,
Athens, GA 30602 (Sanderson); and Twin Cities Animal Reha-
bilitation Clinic, 12010 Riverwood Dr, Burnsville, MN 55337
(Tomlinson). Dr. Daristotle’s present address is 4272 State Rte
732 W, Eaton, OH 45320.
Address correspondence to Dr. Lepine (allan.lepine@effem.com).
Jan Bellows, DVM; Carmen M. H. Colitz, DVM, PhD; Leighann Daristotle, DVM, PhD;
Donald K. Ingram, PhD; Allan Lepine, PhD; Stanley L. Marks, BVSc, PhD;
Sherry Lynn Sanderson, DVM, PhD; Julia Tomlinson, BVSc, PhD; Jin Zhang, PhD
68 Vet Med Today: Reference Point JAVMA, Vol 246, No. 1, January 1, 2015
lying disease or abnormality. To that end, the present
report reviews some of the most common health-relat-
ed changes observed in older dogs as they age.
General Physical Changes
Associated with Aging
Typical physical changes associated with aging in
older, healthy dogs manifest as changes in behavior, ap-
pearance, and daily function, and it is these changes that
are most often noticed by pet owners. Typical behavioral
changes include changes in sleep cycle, responses to ver-
bal commands, and interactions with family and other
pets, which could reflect functional changes in cognitive
and behavioral health. Appearance changes include a
gray, dull, dry coat; loss of muscle mass; and develop-
ment of cataracts and nuclear sclerosis, which could re-
flect functional changes in skin and coat, weight, body
condition, and vision health. Functional changes include
decreased activity and mobility and decreases in vision,
smell, and hearing, which could reflect functional chang-
es in musculoskeletal system and special senses health.
These changes can happen in the absence of any disease
process as part of normal aging.
Cognitive and Behavioral Changes
Age-related changes in the cognitive and behavior-
al domains can be expected in most dogs with advanc-
ing age. Some of the changes that occur in aged dogs
without underlying systemic disease include changes
in cognition, affect, sleep patterns, general activity, and
motor performance; many of these changes likely result
from underlying neurodegenerative processes.12–14
Formal, laboratory-based methods for assessing
age-related changes in cognitive behavior in dogs have
expanded greatly over the past 2 decades. Using meth-
ods adapted from cognitive assessment techniques in
nonhuman primates, Studzinski et al15 and Tapp and
Siwak16 developed the Toronto General Test Apparatus
to identify cognitive impairment in dogs and evaluat-
ed age-related changes in cognitive abilities in Beagles
across several cognitive domains. Age-related declines
were reported in spatial memory, executive function,
and concept learning. What emerged from these studies
was the observation that older dogs could be separated
into impaired and unimpaired animals. The perfor-
mance of unimpaired dogs generally resembled that of
their younger counterparts, whereas impaired dogs had
notable impairments in 1 or more domains of behav-
ioral performance. Impairments were also predictive of
altered sleep-wake cycles, an increased likelihood of be-
havioral stereotypies, and decreased social contact with
humans, which are consistent with behavioral changes
reported in aged pet dogs.14 By contrast, unimpaired
aged dogs had behavioral patterns that differed from
those of both young and age-impaired dogs. Compared
with young dogs, unimpaired aged dogs showed lower
levels of activity as well as a shift from spending a lot of
time interacting with humans to simply spending more
time near humans.14
Analyses of biochemical and anatomic aspects
of aging in dogs have revealed underlying neurologic
changes related to cognitive and behavioral perfor-
mance.14,15,17–21 Further investigation of these changes
found a correlation between cognitive disorders in aged
dogs and the accumulation of oxidative damage in brain
cells.18,22 The brain appears to be particularly suscep-
tible to the damaging effects of oxygen-free radicals.23
Overall, these findings suggest that biological processes
of brain aging that affect the behavior of older dogs can
start as young as 7 to 8 years of age.14
Skin and Coat Changes
With advancing age, several changes occur in the
skin and hair coat of dogs. Cellular atrophy increases in
both the epidermis and dermis. Follicles may also atro-
phy, resulting in areas of hair loss.24 The skin loses elas-
ticity and becomes less pliable as a result of increased
calcium content and pseudoelastin in the elastic fibers.
This loss of elasticity is often accompanied by hyper-
keratosis of both the skin and hair follicles. Loss of me-
lanocytes in the hair follicles and reduced activity of
the enzyme tyrosinase result in the production of white
hairs, which are often observed around the muzzle and
face of older dogs.25 Changes in sebum production in
older animals can result in scaly skin and cause the hair
coat to become dry and dull. Highly sulfated GAGs are
present in the basement membranes of hair follicles,
and their concentration increases with age. A recent ret-
rospective study26 documented that older dogs are more
likely to have a diagnosis of cutaneous neoplasia, with
10 to 15 years being the most frequent age range and
lipomas, adenomas, and mast cell tumors representing
the most common types.
Changes in Body Weight and Condition
As animals age, their basal metabolic rate naturally
slows. This decline is caused primarily by proportional
changes in body composition that include decreased
lean tissue and water contents and increased fat con-
tent. For example, a study27 comparing young and old
dogs reported that the body fat percentage of young
adults was between 15% and 20%, while that of older
dogs was between 25% and 30%. Most, but not all, dogs
voluntarily reduce physical activity as they enter their
senior years. It is estimated that a dog’s total daily en-
ergy requirements may decrease by as much as 30% to
40% during the last third of its life as a result of reduced
activity and decreased metabolic rate.28 For these rea-
sons, some aging dogs are at increased risk for becom-
ing overweight. However, a greater proportion of dogs
> 12 years of age are underweight, compared with pro-
portions for other age groups.29 This may be related to
age-related sarcopenia in older dogs.
Some dogs do remain active and athletic well into
their senior years. Because physical activity helps off-
set age-associated losses of lean body tissue, the basal
metabolic rate in older dogs that remain active may not
decrease substantially.
Musculoskeletal Changes
Lean body (muscle) mass and bone mass decrease
as dogs age. Both the number and size of myocytes de-
crease with age.
JAVMA, Vol 246, No. 1, January 1, 2015 Vet Med Today: Reference Point 69
Sarcopenia is a syndrome seen during aging in the
absence of disease.30,31 The current definition of sarco-
penia in people proposed by the European Working
Group on Sarcopenia in Older People is “a syndrome
characterized by progressive and generalized loss of
skeletal muscle mass and strength with a risk of ad-
verse clinical outcomes, such as physical disability,
poor quality of life, and death.”30 In people, sarcopenia
is associated with increased mortality rate and adverse
effects on muscle strength, immune function, and qual-
ity of life.30,31 Although little information on the effects
of sarcopenia in aging dogs is available at this time, it is
a recognized syndrome in aging dogs, and there is every
reason to believe that its effects on dogs are similar to
those reported in people. A recent unpublished studya
of Labrador Retrievers found that healthy geriatric dogs
(> 8 years of age) had significantly lower mean epaxial
muscle area than did healthy young dogs (1 to 5 years
of age).
Protein requirements sufficient to support protein
turnover may actually increase in older dogs.32 A study29
comparing protein requirements in young versus older
Beagles showed that older dogs required approximately
50% more protein than did young dogs to maintain ni-
trogen balance and maximize protein reserve. In addi-
tion, protein turnover was reduced in older dogs, even
at the highest level of protein fed. Failure to recognize
these nutritional needs as dogs age can accelerate the
weight loss and sarcopenia that occur in geriatric dogs.
The cortices of the long bones become thinner, less
dense, and brittle as dogs age.33,34 The composition of
the articular cartilage matrix also changes with age.
Specifically, a reduced number of chondrocytes leads
to decreased production of GAGs, type 1 collagen, and
chondroitin sulfate.33,34 As a result, aging cartilage grad-
ually becomes less resilient and has limited ability to
regenerate in response to intense activity or trauma.
Changes in the Special Senses
Advancing age may lead to a general decline in a
dog’s ability to react to stimuli and to changes in the
special senses, including vision, hearing, and olfaction.
The most common age-related change in the eyes
of dogs (especially those that are > 6 years of age) is
development of nuclear (lenticular) sclerosis, which
appears as bilateral bluish-gray haziness in the nucleus
of the lens.35,36 It is caused by compression of existing
lens fibers as a result of new fiber formation, leading to
increased density of the lens and an increase in the re-
fractive index of the lens nucleus. Although many dog
owners confuse the resulting bluish haze with cataracts,
nuclear sclerosis does not usually affect a dog’s vision,
except in severe cases. Night vision loss is gradual and
very common in aging dogs; however, most owners and
veterinarians blame the lens changes. Some dogs with a
gradual onset of vision impairment do not demonstrate
signs of these changes until their hearing is diminished,
which illustrates the importance of hearing over vision
in dogs.
Hearing impairment caused by cochlear degenera-
tion is common in older dogs.37 Changes seen morpho-
logically are quantitatively and qualitatively similar to
those that occur in aging humans.37 Although there are
generally no direct health risks associated with hearing
loss, owners are often acutely aware of these changes
and may be concerned for their dog’s safety and quality
of life. In some dogs, age-related changes in cognitive
function may manifest as apparent hearing loss.
Clinical changes in the sense of smell have not
been documented in dogs as a manifestation of ag-
ing, although pathological changes have been demon-
strated. Because dogs and humans age similarly, it has
been hypothesized that cognitive impairment and ol-
factory function may be linked in dogs, as they are in
humans.38,39 In fact, impaired olfactory function is asso-
ciated with the risk of developing cognitive impairment
in humans.40 On the basis of published data, it would be
logical to assume that olfactory function in dogs would
be diminished with advancing age. In a study41 of dogs
> 14 years of age, olfactory epithelium was atrophied,
as was the olfactory nerve layer. In addition, there were
age-related vascular amyloidosis, astrocytic gliosis, and
ubiquitin deposits within the olfactory bulb.41 An inter-
esting difference between human and murine olfactory
bulbs and canine olfactory bulbs is that dogs do not
have β-amyloid deposition in this location, despite hav-
ing it elsewhere in the cerebral cortex.41–44 β-Amyloid has
been found in the olfactory epithelium of aging dogs.45
To clinically evaluate changes in olfaction in aging dogs,
researchers in 1 study39 developed a novel paradigm to
evaluate odor discrimination in dogs and identified a
weak, though not significant, decline in odor discrimina-
tion with age. However, the paradigm needs to be evalu-
ated with a larger group of dogs as well as with untrained
dogs to rule out artifacts before any conclusions can be
made. Nevertheless, given clinical information for other
species, the histologic data, and the preliminary clinical
data for dogs, it is likely that a dog’s sense of smell di-
minishes with age.
Oral and Gingival Changes
In dogs that do not have evidence of plaque, calcu-
lus (tartar), gingivitis, or periodontal disease, there are
no changes to the visual appearance of the gingiva and
dental hard structures as dogs age. Plaque normally at-
taches daily on the crowns of teeth unless mechanically
or chemically removed. Calcium and phosphorus in the
saliva then mineralize the plaque to produce calculus.
It is common to find plaque and calculus on the teeth
of healthy aged dogs.
Mouth size is a significant risk factor for periodon-
tal disease in dogs. Clinically, larger aged dogs may
have healthy mouths and teeth with little plaque and
calculus accumulation, while smaller dogs may have
greater accumulations of plaque and calculus, are more
likely to develop periodontal disease at an early age,
and tend to show more severe disease, compared with
larger dogs.46 Reduced jaw size and crowding of teeth
may be predisposing factors for dental disease in small-
er dogs. In addition, toy-breed dogs are more likely to
have malocclusion problems, which may facilitate the
deposition of subgingival plaque that is more difficult
to remove through either chewing or home care. As
periodontal disease progresses, there is destruction and
70 Vet Med Today: Reference Point JAVMA, Vol 246, No. 1, January 1, 2015
loss of alveolar bone along the roots of teeth. Because
smaller dogs have a lower ratio of mandibular size to
tooth volume, compared with the ratio in larger dogs,
the loss of bone has a greater impact.47
Owner intervention in preventing plaque accu-
mulation can have a major impact on the establish-
ment and progression of periodontal disease in dogs.
If the owner strictly controls plaque, the periodontium
remains healthy and the teeth should remain well-
anchored in their alveoli. Conversely, if the owner does
not establish a plaque control regimen, periodontal dis-
ease will usually occur, leading to gingival inflamma-
tion and, eventually, tooth loss.
Gastrointestinal Tract Changes
With advancing age in dogs, several structural and
functional changes take place in the GI tract. These in-
clude reduced salivary and gastric acid secretion; de-
creased villus size, rate of cellular turnover, and colonic
motility; and alterations in the intestinal microbiota.28
One study48 found that age and dietary fructooligosac-
charide supplementation affect the intestinal microbiota
in dogs. Another study49 found that the microbiota in
the large bowel changes as dogs age. In a third study,50
the authors found a difference in metabolic activity in
the feces of 4-year-old dogs, compared with that in feces
of 10-year-old dogs. Age-related changes in fermentation
products in that study50 suggested an alteration in bacte-
rial metabolic activity or in the rate of intestinal absorp-
tion of these compounds. Although it has been theorized
that aging of the GI tract leads to a decreased ability to
digest and absorb nutrients, studies51–53 of healthy older
dogs indicate that most dogs appear to maintain diges-
tive efficiency as they age. This makes calculating en-
ergy provisions for aged dogs relatively straightforward.
Because maintenance energy requirement decreases by
approximately 20% and energy digestibility remains
constant, aged dogs should be offered a reduction in
energy equivalent to an approximately 20% decrement,
although individual variations in metabolic rates exist.54
Using radiopaque markers and radioisotopic meth-
ods, researchers55 have demonstrated slowing of gastric
emptying after consumption of large solid meals and a
delay after consumption of large liquid meals in older
people. Results of a study56 involving rats support the
concept that changes in the aging GI tract result in in-
creased satiety. The effects of age on the gut microbi-
ota have been well studied in people. A recent study57
showed that although microbial composition and gut
ecosystems are similar in young adults and seniors, they
differ significantly from those of centenarians. Changes
in the microbiota of centenarians are associated with
inflammaging (a chronic, systemic inflammatory state)
and a reduction in symbiotic bacterial species that have
anti-inflammatory properties.
The liver is the central organ in the regulation of
nutrient metabolism, xenobiotic metabolism, and de-
toxification. Evidence from humans and rodents has
indicated that aging leads to marked changes in liver
structure and function.58 The aged liver is characterized
by decreases in weight, blood flow, regeneration rate,
and detoxification rate, which are related to an increased
risk of liver abnormalities in the elderly.58 Aged dogs are
affected by many of the same chronic hepatic disorders
seen in elderly humans, with age-related alterations in
liver function influenced by diet. Molecular microarray
analysis of liver tissue from aged and young-adult dogs
revealed that genes related to inflammation, oxidative
stress, and glycolysis were upregulated, whereas genes
related to regeneration, xenobiotic metabolism, and
cholesterol trafficking tended to be downregulated in
aged liver tissue.59
In humans, age-related changes in exocrine pancre-
atic secretion include decreased flow rates and dimin-
ished production of bicarbonate and enzymes; howev-
er, functional and structural changes do not occur in
everyone, nor do they progress continuously.60 These
changes are generally not associated with clinical mani-
festations and do not require substitution treatment
because the reduction in enzyme secretion is typically
well below the 80% to 90% decrease in exocrine func-
tion at which maldigestion occurs.60–62 There is also a
decrease in secretin-stimulated secretions.60–62
Cardiac Changes
Normal vascular changes that occur with age in
dogs include hyaline thickening of blood vessels and
increased calcium deposition in the intima of the aorta
and sections of the peripheral arteries.63 Together, these
changes contribute to an increased load on the heart,
which can eventually lead to the development of con-
gestive heart failure.
Beginning in midlife, cardiac output gradually de-
creases and can decrease by as much as 30% in geriatric
dogs.63 Maximum heart rate and oxygen consumption
during exercise also decrease as animals age. For exam-
ple, a study64 that compared cardiovascular responses
during exercise between young and old dogs reported
that aging was associated with a loss of cardiovascular
reserve and adaptability. These changes are presumed
to contribute to cardiovascular disease in older dogs.
The effects of aging on contractile performance,
stiffness, and contraction time of the left ventricle
were evaluated in 8 young (mean ± SEM age, 27.5 ±
2.5 months) and 7 old (128 ± 20.5 months) Beagles.65
A major finding of this study showed that increasing
age was associated with an increase in the stiffness of
the left ventricle, both in systole and diastole, as well
as a prolonged duration of contraction. A more recent
study66 evaluated the effects of age on transmitral and
pulmonary venous flow in client-owned dogs compris-
ing 27 breeds that ranged from very young (3 months
of age) to very old (19 years of age). Results indicated
that a gradual decrease in the rate of left ventricular
relaxation, an increase in myocardial stiffness, and an
enhanced late diastolic filling occur with aging in dogs.
Although there are limited studies in dogs evaluating
the effects of aging on cardiac function, there do appear
to be some age-related changes that could adversely af-
fect the ability of older dogs to respond to cardiac stress
in the same way as younger dogs.
Respiratory Tract Changes
Aging changes in the respiratory system have been
well characterized in humans and have been document-
JAVMA, Vol 246, No. 1, January 1, 2015 Vet Med Today: Reference Point 71
ed, albeit to a lesser extent, in dogs as well. In hu-
mans, major age-related changes include decreases
in pulmonary elasticity, respiratory muscle strength,
and chest wall compliance.67 Alterations in pulmonary
immune cell number and function, reduced diffusing
capacity across the alveolar-capillary membrane, and
dysfunction in pulmonary β-adrenoreceptors and air-
way reactivity have also been associated with aging in
humans.68
Similar changes are considered likely to develop
with advancing age in dogs. Pulmonary alveoli enlarge
and coalesce, leading to reduced lung elasticity and
decreased surface area for gas exchange.69 In addition,
control of breathing has been shown to be altered with
age in dogs, with decreases in ventilation and responses
to hypoxia during slow-wave sleep.70
For the most part, even with this decrease in criti-
cal ventilatory functions, the respiratory system of
older humans is capable of maintaining adequate gas
exchange,71 and the same appears to be true for older
dogs.
Renal and Urinary Tract Changes
Although a gradual decline in renal function is nor-
mal in older animals, a substantial loss of functioning
nephrons must occur before changes in renal function
become evident by routine assessment. With the excep-
tion of acute renal damage, most damage that occurs
in the kidneys as dogs age is irreversible, and the heal-
ing of irreversibly damaged nephrons occurs by means
of replacement fibrosis.72,73 Renal histopathologic
preparations usually show some combination of a loss
of tubules with replacement fibrosis and mineraliza-
tion, glomerulosclerosis and glomerular atrophy, and
foci of mononuclear cells (small lymphocytes, plasma
cells, and macrophages) within the interstitium. These
changes are nonspecific, and as a result, the underlying
cause of the renal damage is usually unknown. Com-
pensatory hypertrophy occurs in the remaining viable
nephrons and creates a large functional reserve early on
in the process.
A study74 conducted over a period of 13 years eval-
uated clinical changes in renal function associated with
age in Beagles. Results showed that nephrosclerosis was
the most frequently diagnosed kidney lesion in older
dogs. The data from that study also indicated that nor-
mal kidney aging may lead to nephron loss of up to
75% before clinical signs or conventional biochemical
changes occur in older dogs. Animals with < 75% loss
may be more susceptible to renal insult than younger
animals still possessing renal reserve capacity.
Alterations in renal cortical and medullary GAGs
are also seen in aging dogs. Glycosaminoglycans are
among the most highly negatively charged molecules
known, and their presence in the glomerular basement
membrane helps maintain the membrane’s charge bar-
rier properties, which prevent protein from crossing
from the glomerulus into the glomerular filtrate.75 Hy-
aluronic acid in the extratubular stroma of the medulla
contributes a gelatinous support for the tubular struc-
ture of the nephron and may slow translocation of so-
dium in the renal tubules. One study75 evaluated GAG
composition of the renal cortex and medulla in healthy
younger and older dogs. Results showed a significant
reduction in the heparan sulfate content of the cortex
(where all glomeruli are located) and a decline in hy-
aluronic acid content in the medulla in aging dogs. In
the renal cortex, heparan sulfate concentration, which
is the predominant GAG, gradually increased until the
sixth year of age and then sharply decreased as dogs
grew older. Heparan sulfate and hyaluronic acid were
present in equal proportions in renal cortexes of 1-
and 3-year-old dogs; however, in the renal cortexes of
10-year-old dogs, heparan sulfate formed only 30% of
the total GAG content, which is only 0.75 times the
hyaluronic acid content. The reason for the alterations
in the GAG composition in the renal cortex as dogs age
is not clear, but it may explain the frequency of pro-
teinuria related to aging in dogs. In the renal medulla,
chondroitin sulfate concentration, which forms a small
proportion of the total GAGs, remained unaltered in
young versus aging dogs. However, medullary hepa-
ran sulfate concentration, which formed a third of the
total GAG content in 1- and 3-year-old dogs, steadily
decreased as dogs aged. By 10 years of age, heparan sul-
fate formed only 14% of the total GAG content, and
the ratio of hyaluronic acid to heparan sulfate, which
is approximately 1.0 in younger dogs, increased to 3.9
in aging dogs.
Changes to the Endocrine System
Age-related alterations in adrenal cortex secretion,
serum cortisol and aldosterone concentrations, and
HPA axis regulation have been reported in dogs.76–78
Breed, dietary habits, and the level of physical activ-
ity can influence adrenal and renal parameters as well
as serum electrolyte concentrations and arterial blood
pressure.79 In addition, sex-related differences and hor-
mone cycle influences in healthy older dogs have been
reported.80
The influence of aging on adrenal responsiveness
in dogs has been well studied, with studies77,78,81 show-
ing that aging is associated with increased HPA activity,
characterized by increased plasma ACTH and cortisol
concentrations and increased urinary cortisol excre-
tion. Strasser et al78 theorized that increased cortisol
concentration could point to an “age-related hyperad-
renocorticism and indicates a reduced stress resistance
in older animals to equal stress than younger animals.”
Other authors have assumed that sensitivity to negative
glucocorticoid feedback at the pituitary, hypothalamus,
and hippocampus levels is reduced in aging dogs.77
Basal activity of the HPA axis is controlled by miner-
alocorticoid receptors (predominantly located in the
hippocampus) and glucocorticoid receptors (located
in the pituitary gland and the hippocampus). The loss
of mineralocorticoid and glucocorticoid binding sites
with aging may explain the altered feedback regulation
documented in elderly dogs. Healthy dogs between 11
and 14 years of age had a marked reduction in miner-
alocorticoid receptor-binding capacity (expressed as a
percentage of the corresponding levels in dogs between
18 and 24 months of age) in the dorsal hippocampus,
ventral hippocampus, septum, and hypothalamus.77
The effects of advancing age on serum concentra-
tions of T4 and TSH, on T4 responses to TSH, and on
72 Vet Med Today: Reference Point JAVMA, Vol 246, No. 1, January 1, 2015
TSH responses to thyrotropin-releasing hormone have
been studied in prepubertal, adult, middle-aged, and
old Beagles.82 Serum T4 concentrations were highest in
puppies and decreased by 40% in older dogs.82 A lon-
gitudinal study completed over the lifetime of healthy
Labrador Retrievers identified age-related decreases
in total triiodothyronine (T3), T4, and free T4 concen-
trations and age-related increases in T4 autoantibody
concentration.83 Baseline serum T4 concentration is
lower in some breeds, most notably sight hounds such
as Greyhounds84 and northern breeds such as Siberi-
an Huskies. Thus, a serum total T4 concentration that
is less than the lower reference limit can be a normal
age- or breed-related phenomenon and should not be
misinterpreted as evidence of hypothyroidism. In dogs,
serum T4 concentration can also be suppressed by a va-
riety of factors, including nonthyroidal illness and ad-
ministration of medications such as prednisone, pheno-
barbital, and sulfonamide antimicrobials.85 The reasons
for the reduction in T4 concentrations in older dogs are
not well-understood, and this decrease could be relat-
ed to decreased responsiveness of the thyroid gland to
TSH, fibrosis or atrophy of the thyroid gland, decreased
biological activity of TSH, and concurrent illness.
The pancreas and pancreatic function may also be
affected by age. Age is a significant risk factor for glucose
intolerance and diabetes mellitus in dogs. This may result
from either a reduction in the number of insulin recep-
tors or development of insulin receptor insensitivity.86 In
addition, the change in body fat content that is associ-
ated with aging is strongly and positively correlated with
changes in glucose tolerance. This reduction in insulin
sensitivity may be ameliorated through weight loss or
the prevention of becoming overweight.87 Improved glu-
cose tolerance has been demonstrated with diet restric-
tion in Labrador Retrievers undergoing a lifetime food
restriction trial.83 A 25% reduction in food intake over
the course of the dogs’ lives was associated with lower
mean basal serum glucose concentration (9% lower) and
plasma insulin concentration (33% lower) among the
dogs that were food restricted, compared with values for
their control-fed littermates.
There is also evidence that ovarian (endogenous
estrogen) status contributes to healthy aging.88 Female
Rottweilers tend to outlive male Rottweilers. However,
ovary removal during the first 4 years of life abolished
the female Rottweilers’ survival advantage.
Immune System Changes
The immune system is an interactive network of
cells, proteins, and signaling molecules designed to
provide protection from environmental pathogens, par-
asites, malignant cells, allergens, and toxins.89 Similar
to changes reported in rodents and humans,90 the im-
mune system in dogs undergoes complex remodeling
with advanced age, also known as immunosenescence.
Canine immunosenescence has been studied for more
than 3 decades,91 and various changes in the immune
system can be found in healthy aged dogs (Appendix).
There are fundamental changes in both T-cell– and
B-cell–mediated immunity in aging dogs. It is well-
documented that old dogs (8 to 13 years of age) have
lower lymphocyte proliferative response to specific an-
tigens, including phytohemagglutinin, concanavalin
A, and pokeweed mitogens, compared with responses
in young dogs (2 to 4 years of age).92–95 A study96 of
immune activation of lymphocytes in 40 young (< 1.5
years of age) and old (> 7 years of age) Fox Terriers
and Labrador Retrievers found that both breeds dem-
onstrated an age-related decrease in their ability to re-
spond to various mitogens, but that the decrease was
greater for Fox Terriers than for Labrador Retrievers.
Aging is also associated with changes in the distri-
bution of lymphocyte subsets in the peripheral blood,
including phenotypic changes in the absolute number,
relative percentage, or ratio of T cells and T-cell subsets
and B cells in the peripheral blood or in the expression
of surface markers of activation or memory in these
subpopulations.84,92,93,97–101
Age-associated changes in humoral immunity are
reflected in the number and function of B cells and
through antibody responses to antigens or vaccina-
tion.92,94–96 Increasing age has been associated with in-
creased production of inflammatory mediators in mice
and humans.102,103 The T-helper 1-to-T-helper 2 ratio
changes to reflect a dominance of the T-helper 1 sub-
population in the peripheral blood as dogs age.104 There
is also evidence of no significant changes in tumor ne-
crosis factor-α activity and increased interleukin-1–like
activity in older female dogs (age range, 8 to 13 years).95
On the other hand, the innate immune system is
apparently less vulnerable to age, compared with the
acquired immune system. There are subtle or no chang-
es in natural killer cell activity and polymorphonuclear
leukocyte phagocytic activity with age.94,95,105
Conclusions
It is readily apparent that considerable changes oc-
cur in virtually every body system of dogs with advanc-
ing age. Some of these changes can greatly affect the
health and well-being of older dogs and have a tremen-
dous impact on their owners, both from the standpoint
of cost of management and from the viewpoint of the
daily pet-owner relationship. An appreciation of aging
in dogs is critical for both clinical and research reasons.
In this regard, it is imperative to be able to distinguish
between what should be considered normal versus un-
healthy aging changes. This distinction would clearly
impact clinical management of aging dogs in that man-
agement could be adjusted on the basis of normal ag-
ing expectations. Research efforts in dogs could be fo-
cused on evaluating the effects of various interventions
in healthy aging dogs and older dogs with evidence of
disease. Additional effort is needed to define the clinical
assessments required to differentiate healthy aging from
disease for each of the systems identified.
a. Hutchinson D, Sutherland-Smith J, Watson AL, et al. Waltham Centre
for Pet Nutrition, Leicestershire, England: Unpublished data, 2012.
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Appendix
Summary of studies of immunosenescence in dogs.
Breed Mean age or age range (y) Findings
Fox Terrier96 11.5 Decreased mitogen responses to phytohemagglutinin, pokeweed mitogen,
Labrador Retriever96 9.6 and concanavalin A
Beagle, Labrador Retriever, 12.1
and other breeds92
Labrador Retriever93 Lifetime
Labrador Retriever94 9.1
German Shepherd Dog95 8–13 Decreased mitogen response to phytohemagglutin
Beagle, Labrador Retriever, 12.1 Higher CD8+, lower CD4+:CD8+
and other breeds92
Beagle101 > 5 Higher CD8+, no change in CD4+, lower CD4+:CD8+, higher B cell
Labrador Retriever93 Lifetime Lower CD8+, higher B cell
Fox Terrier96 11.5 Decreased antibody response to sheep RBCs
Labrador Retriever96 9.6 No changes in antibody response to sheep RBCs
Labrador Retriever94 9.1 No changes in antibody response to protein antigen
German Shepherd Dog92 12.1 No changes in antibody response to vaccine; no difference in IgM and IgG
German Shepherd Dog95 8–13 No changes in IgG
German Shepherd Dog95 8–13 Decreased interluekin-2, no changes in tumor necrosis factor-α, increased
interleukin-1–like activity in female dogs
Beagle104 > 8 Inclined to T-helper 1 dominance
Labrador Retriever105 Lifetime No difference in NK cell activity and polymorphonuclear leukocyte phagocyte
activity
Labrador Retriever94 9.1 No difference in NK cell activity
German Shepherd Dog95 8–13 No difference in polymorphonuclear leukocyte phagocytic activity and
increased NK cell activity in female dogs
NK = Natural killer.
