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Geropathology is a common denominator for multispecies research in geroscience, from insects to nonhuman primates
* Corresponding author: Warren Ladiges
Mailing address: Department of Comparative Medicine, Division of Gerontology and Geriatric Medicine, Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Email: wladiges@uw.edu
Received: 25 March 2026 / Accepted: 25 March 2026 / Published: 31 March 2026
DOI: 10.31491/APT.2026.03.202
Abstract
Geropathology embraces geroscience by defining anatomic and molecular aspects of aging as a basis for gaining a better understanding of how we age, and embellishes the identification of specific targets for gerotherapeutic intervention. Anatomic geropathology in various animal models of aging is based on microscopic evaluation of all age-related lesions so that lesion severity can be assigned a score as a quantitative value in a specific organ. Laboratory mice, nonhuman primates, pet cats, and house crickets have all been shown to develop similar age-related lesions that increase in severity with increasing age. These observations suggest that geropathology serves as a common denominator involving the cellular deterioration of tissues with increasing age in a diverse animal population from insects to high order mammals such as nonhuman primates. Geroscience, as an evolutionary-conserved approach to prevent the rapid progression of aging and age-related conditions in older people, is therefore supported by geropathological interrogation.
Keywords
Geroscience, geropathology, age-related lesions, laboratory mice, nonhuman primates, pet cats, house crickets
Geroscience assumes all diseases that affect primarily older adults have a common and major underlying cause of
declining function and resilience that is part of the aging
process. Geropathology embraces geroscience by defining anatomic and molecular aspects of aging as a basis for
gaining a better understanding of how we age, how we develop age-related diseases, and the emergence of specific
targets for gerotherapeutic intervention [1].
Anatomic geropathology is based on microscopic evaluation of all age-related lesions so that lesion severity can be
assigned a score as a quantitative value in a specific organ.
Therefore, increases in lesion severity in individual organs
can be followed with increasing age. This approach is in
line with the geroscience concept that manipulation of aging will simultaneously delay the appearance or severity
of major diseases with a decrease in the severity of histological lesions because of the same underlying major risk
factor: aging and the multiple processes involved in aging.
Ideally, studies to advance a geropathology lesion grading
approach would be carried out in humans. However, from
a geropathology perspective, clinical studies can be challenging because of a lengthy lifespan and lack of access
to tissues from human organs. Therefore, animal models
are being relied on to partially overcome these challenges.
An ideal animal model of human aging should exhibit
comparable naturally occurring diseases, share the same
environment, have a heterogeneous background, and be
amenable to therapeutic intervention studies that would
accurately predict positive results in people. Rodents, and
to a lesser extent, nonhuman primates, are used extensively in geroscience research studies. These species have
many advantages for modeling a wide variety of agerelated conditions and biology of aging concepts.
The mouse is one the most widely used mammalian species in geroscience research. An anatomic geropathology
grading approach has been developed and validated in
mice as a useful tool to study aging and the relationship
of age-related histopathologic lesions in specific organs to
age related disease [2]. Geropathological interrogation of
individual mouse organs provides a powerful look at the
morphologic changes associated with increasing age in
an organ-dependent manner [3]. In addition, lesion grading provides insights into how different organs respond to therapeutic drugs based on changes in severity of lesion
scores.
Even though mice develop a number of age-related conditions, some are still not well aligned with several common age-related ailments observed in people. Nonhuman
primates (NHPs) share more similarities in aging and
spontaneous chronic diseases with humans than mice, so
are considered an excellent translational model of aging.
A preliminary geropathology grading platform has been
described for rhesus macaques and common marmosets
[4]. Lesion severity in specific organs has been shown to
increase with increasing age in both species similar to the
mouse.
Several species are not as commonly used in geroscience
research as mice and NHPs, but have outstanding characteristics for modeling aging in humans. Pet cats share the
same environment and are exposed to the same environmental conditions as humans. In addition, comorbidities
occurring in humans are common in pet cats and provide
a rich venue for investigating the impact of aging on risk
for developing chronic disease conditions and the role
multiple pathways of aging may be playing [5]. Lesion severity in specific organs has been shown to increase with
increasing age in pet cats similar to mice and NHPs.
Another species that is just being developed as an animal
model of aging is the house cricket [6]. The house cricket
has a relatively short lifespan of 10 to 12 weeks, with
distinct developmental stages that can be compared to
life stages of humans. Physiological processes are wellcharacterized and maintenance in laboratory settings is
straightforward and inexpensive. Therefore, the house
cricket is a practical model for studying morphological
and functional deterioration associated with aging. Interestingly, geropathological assessment shows that house
crickets develop lesion severity with increasing age just
like pet cats, NHPs and mice (Klug, Liao, and Ladiges,
unpublished observations). Organs are rudimentary but
well compartmentalized, and in older crickets show a
number of the same lesions seen in mammals.
These published and unpublished observations suggest
there is a common thread involving the cellular deterioration of tissues with increasing age in a diverse animal
population from insects to high order mammals such as NHPs. Therefore, geropathology is a base-line denominator for helping establish geroscience as an evolutionaryconserved approach to prevent the rapid progression of
aging and age-related conditions in older people.
Declarations
Availability of data and materials
Not applicable.
Financial support and sponsorship
None.
Conflicts of interest
Warren Ladiges is a member of the editorial board of Aging Pathobiology and Therapeutics. The authors declare that they have no conflicts and were not involved in the journal’s review or decision regarding this manuscript.
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