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Physiology, Aging Cite this Page
Bronson Flint; Prasanna Tadi.
Author Information
Last Update: November 21, 2021.
In this Page
Introduction
Introduction Go to: Issues of Concern
Although aging is an almost universal truth that we all experience throughout our lives, it is vital Cellular
that clinicians understand both the clinical and epidemiological relevance of this process.
Development
Senescence brings a variety of changes across the spectrum of the body’s systems, which require
special care and management. Estimates are that the number of adults older than 65 will reach Organ Systems Involved
upwards of 88.5 million by 2050, which will surely place a higher demand for healthcare providers
Function
and hospital systems.[1] While technology has allowed for a massive expansion of the capabilities of
modern medical science, many side effects have appeared over time, of which not all have Mechanism
developed at the same rate as medical science in general—not the least of which is our overall Related Testing
prolonged life expectancies. This implies a particular impetus to develop new screening methods,
cope with protracted management of disease which might have proved fatal quite quickly before the Pathophysiology
advent of certain biomedical technologies, and to promote and develop health and wellness lifestyle Clinical Significance
measures at an early age to avoid the pitfalls of chronic illness and disease later in life.[2]
Review Questions

Issues of Concern Go to: References

Biologically speaking, aging—or senescence, which more accurately depicts the processes occurring
from a biological standpoint—is a chronic, normal culmination of the loss of specific regenerative
and bioprotective mechanisms that occur over time in an organism.[3] Expanding this idea to the Related information
human being, we can clearly begin to ascertain that aging by default necessitates a pro-disease state. PMC
This article will attempt to characterize some of the most concerning issues that arise as a result of PubMed
the normal aging process, without, of course, being an entirely exhaustive list of all possible
manifestations.

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Endocrine - Diabetes mellitus Risks [StatPearls. 2022]

Urological/Gynecologic - Urinary tract infections, urogenital cancer, cervical cancers, breast See reviews...
cancers, prostate cancer See all...
Special Senses - Presbycusis, presbyopia, cataract, macular degeneration, glaucoma

Gastrointestinal - Malabsorption, GI malignancies, bowel obstruction, diverticular disease Recent Activity

Turn Off Clear
Other special consideration - Independence, falls, elder abuse and neglect, psychiatric
concerns, skin breakdown, skin tears Physiology, Aging - StatPearls

Cellular Go to: See more...

At the cellular level, the primary aging-related mechanisms occur as cell proliferation slows
eventually to the point of total cessation. Additionally, some literature suggests that increased
protein production, apoptotic resistance, and alterations in cellular biochemical activity combined
with an accumulation of many like cells in this state, as mentioned above, also contribute to the
phenotype we associate with aging. As we age through young and middle adulthood, the overall
amount of these senescent cells within our bodies remains relatively low and manageable to
overcome by the body’s still higher number of cells, which are not yet senescent and functioning in
line with normal physiology. It is the point at which we cross the threshold of capacity relative to the
number of senescent cells within our body and then their subsequent accumulation in our tissues that
we begin to see disease associated with aging. For instance, some hold that the development of
osteoarthritis is associated with accumulations of senescent cells within the affected joint regions,
leading to subsequent degeneration and eventually decreased function of that joint and its usefulness
in our mobility.[4]

Development Go to:

From the moment we enter life, our aging process begins. It is a slow, chronic process, the origins of
which are not necessarily well understood but universally accepted. Several theories have emerged
as to the origin story of our aging processes. Some hold that aging is a sort of biologically
“programmed” mechanism that occurs because extremely advanced age holds little evolutionary
benefit, the idea being that if organisms could age for some prolonged-time period, they would be
yet another competitor for scarce resources that are also being pursued by a younger generation of
organisms mostly thought of as being more capable of reproduction than their aged counterparts.
[5] By extrapolating this idea of programmed senescence to human beings specifically, it has been
proposed time over that our aging occurs resulting from genetically pre-programmed hormonal
mediation. That is, growth hormone and the insulin pathway, which are well-understood to be
associated with development, are controlled by the neuroendocrine system and can play a central
role in the mediation of an organism’s aging process via various forms of gene expression and
subsequent hormonal fluctuance.

Yet another theory that underpins the development of aging is that of accumulations of damage at
the cellular level throughout our lifespan. More specifically, to this point, the suggestion is that the
generation of reactive oxygen species and the resulting methylation changes in our DNA could be
the underlying mechanism by which we progress into aging.[6] This potential mechanism of aging is
also closely tied to the development of reactive oxygen species, which results in oxidative damage.

Organ Systems Involved Go to:

Virtually all organ systems are involved in the particular physiologic changes associated with aging.
Cumulatively, the loss of cell turnover, decreased function of mucous membranes, cachexia and
skeletal muscle mass wasting, increased atherosclerotic decrease in vascular compliance, and
cerebral atrophy eventually all contribute to the variety of changes we see in aging. It is essential to
distinguish the normal processes of aging from those pathologic changes that occur in the setting of
disease but are markedly more drastic due to the decreased or total loss of compensatory
mechanisms.

Specifically, some of the many changes which occur are listed by organ system below.

Neurological

Abnormal compensatory mechanisms predispose individuals to neurodegeneration and dementia,

Parkinson disease, and overall cerebral atrophy are observable in aging individuals.[7]

Gastrointestinal

Changes in taste and smell, altered gut motility, and intestinal microbiota abnormalities can lead to
age-related anorexia and subsequent caloric and/or nutritional deficiency. The weakening of smooth
muscle in the intestinal tract can promote the development of diverticular disease and can play a role
in bowel obstructions or constipation. Decreased metabolic activity, specifically in the liver, can lead
to alterations in drug metabolism.[8]

Renal

Aging leads to a reduced number of functional glomeruli and an increased prevalence of sclerotic
changes within the glomeruli or renal vasculature. Additionally, there is a normal decrease in GFR
observed in advanced age, but this places the elderly at much higher risk for complications in the
event that they develop chronic or acute kidney disease, as they have less functional glomeruli as a
result of normal aging physiology.[9]

Cardiovascular

Aging lowers the threshold for cardiovascular disease development. This is mostly due to a loss of
cardioprotective and compensatory mechanisms that otherwise help to prevent the development of
serious cardiac disease. For example, vascular stiffening, increased left ventricular wall thickness,
myocardial fibrosis, calcification of valves and their related structures, as well as decreased aerobic
tolerance and increase of problematic cardiomyocyte remodeling all potentially increase risks for
cardiovascular diseases with aging.[10]

Respiratory

Age-related changes in the respiratory system primarily center upon the loss of elasticity and
decrease in chest wall compliance leading to increased work of breathing, as well as increased
residual volume and functional residual capacity. Additionally, decreased strength and function of
respiratory muscles is observable. All of these changes drop an aging patient’s threshold in
compensating for an acute illness or respiratory failure.[11]

Endocrine

Age-related decline in endocrine function can yield various effects within the realm of metabolic and
hormonal control in aging populations. Thyroxin and triiodothyronine secretion decrease, resulting
in overall decreased metabolic activity, circadian rhythms become altered, and patients are prone to
reduced REM sleep. Alterations in glucose metabolism and, specifically, insulin secretion develop
with age, promoting the development of diabetes mellitus in the elderly. Specific sex-linked
endocrine function is impaired or altered with age as well. Women typically experience menopause
in their sixth decade of life, which is accompanied by an increased risk of cardiovascular disease,
loss of bone mass, and atrophy of estrogen-responsive tissue.[12]

Function Go to:

The process of aging is well understood to be part of the natural progression of the human life cycle.
Simply by virtue of cellular degradation combined with the loss of biosynthetic and cellular repair
mechanisms that might have compensated for this degradation in our youth, aging is a chronic and
unavoidable state that we will eventually all enter.

Mechanism Go to:

On a cellular level, aging is believed to result from a variety of factors related to cellular senescence.
The overarching notion is that human cells can only replicate a finite number of times before they
become senescent. Previous research in this field has shown that as a cell divides, telomeres on the
DNA strand become gradually shortened.[13] The mechanism by which this occurs can be
summarized by understanding that the telomeres appear to serve a chromosome-protective role. As
the telomere length decreases, so too are the protective qualities of the proteins, which normally at
the distal ends of the telomere and allow DNA repair enzymes to recognize telomeres amongst sites
of DNA damage. As a result, the loss of telomere length and concomitant loss of these protective
proteins exposes the ends of the chromosomes to damage by DNA repair enzymes.[14] This process
is compounded by DNA repair complex-mediated activation of transcription factor p53, which, in
conjunction with cyclin-dependent kinase inhibitor p21, can result in subsequent senescence of cells
and, ultimately, cessation of their metabolic and replicative functions.[15]

Related Testing Go to:

Tests relevant to aging and its associated physiology are system and patient or pathology-specific.
For example, in an elderly patient with confusion or alterations in neurological status, it might be
valuable to administer the mini-mental state examination (MMSE) or, whereas in a patient of 20
years old with similar symptoms, the underlying pathology is likely, not due to dementia as it would
be in the elderly patient, so different testing would be necessary.[16] Additionally, in patients with
advanced age, certain routine screening tools or tests require implementation due to the unique set of
health concerns experienced at older ages. For example, men should receive digital rectal exams for
prostate cancer screening; women mammography for breast cancer screening, and annual
colonoscopies are a great screening tool to exclude colon cancer in men and women alike. The
purpose of such screening tools is to discover disease as early as possible in its clinical course and
identify unhealthy lifestyles and behaviors for which the patient can then receive counseling.
[17] Such tools are especially valuable in such an aging population as it is well understood that
disease risk increases with age.

Pathophysiology Go to:

Three distinct processes can reasonably explain the pathophysiology underlying the aging process:

Production of Free Radicals

Free radicals are well known in the biochemical world as a normal byproduct of healthy physiology
in well-regulated, relatively small amounts. They exist as a molecule with a single, unpaired valence
electron, rendering them highly reactive in the presence of other substances as they attempt to
interact with other substances in an effort to obtain additional valence electrons and balance the
electron configuration.[18] The exact underlying mechanisms underlying the downstream adverse
effects of free radical generation and subsequent interaction with cellular components is beyond the
scope of this paper, but it bears mentioning that free radicals can denature proteins, destroy
membrane lipids, nucleic acids, and certain organelles such as lysosomes and proteasomes.[19] The
importance of understanding free radical or reactive oxygen species-derived degenerative changes is
that the belief is that accumulated cellular damage via these molecules will—in time—cumulatively
overwhelm the cell’s damage repair mechanisms, leading to the eventual physiologic collapse of
first, the cell, then the whole organism.[18]

Glycation

Advanced glycosylation end-products form when reactions occur between aldehyde groups of
reducing sugars and amino groups of proteins. The formation of these metabolic products occurs in a
fashion dependent on elevated blood glucose.[20] In aging individuals, glycemic control becomes
less regulated, and glucose tolerance can undergo significant alteration. The predominance of
advanced glycosylation end-products can result in such abnormalities as vascular fibrosis, thickened
basement membranes, impaired lipid metabolism, and reduced collagenous elasticity. Furthermore,
advanced glycosylation end-products are associated with the induction of inflammatory responses,
resulting in the release of inflammatory substances and reactive oxygen species, causing further
tissue damage.[18]

Reduced Regenerative Capacity

In healthy individuals, a balance exists between one cell’s apoptosis and the maturation and healthy
development of another cell that essentially takes the place of the first. Researchers believe that
mechanisms within the cell cycle control both the programmed death of a senescent cell but also
signal externally to other cells the need for the development of a new, healthy cell to backfill
whatever metabolic demands the senescent cell might have been meeting. The progression between
stages in the cell cycle is controlled by regulatory proteins, whose function demonstrably declines in
senescent cells compared to younger, healthy cells. The ability of these protein-derived signaling
pathways to communicate the need for cell regeneration and maturation in the healthy, young cells
seems to be reduced in the aging process, while the pro-apoptotic pathway signaling mechanisms
continue to function, leading to a net decline in functional, healthy cells.[18]

Clinical Significance Go to:

The aging process is a natural phenomenon that occurs due to a variety of loosely understood
mechanisms. Via a combination of telomeric shortening, which triggers pro-apoptotic pathways
when sensed in the cell cycle, which subsequently triggers inflammatory mediators and the release
of damaging reactive oxygen species, our bodies and their ability to maintain physiologic
homeostasis degrade with time. Moreover, so too does the body's ability to regenerate or reproduce
healthy cells and tissues as we age. The aging process brings with it phenotypical changes that
clinicians must understand and consider when caring for aging patients.

It is essential to recognize that aging involves a great deal of interplay between lifestyle and
genetics. An individual who maintains a healthy lifestyle, has access to adequate, routine medical
care and screenings, and enters into late adulthood with a clean bill of health will experience a vastly
different aging process than someone who is sedentary, makes poor diet and lifestyle choices, and
has lived with chronic disease before and upon entry into late adulthood.

Aging is relevant to clinical care and management because it often implies underlying derangements
of normal physiology. As an example, this article mentioned earlier that urinary tract infections are
more common in the elderly. Some patients may experience an increased frequency of falls due to
the weakness imposed by their urinary tract infection or their bladder urgency forcing them to
attempt to hurriedly make it to a toilet. Clinicians must remain vigilant of the manifestations of
disease in aging, and likewise, the presentation of physiologic derangements that pose a potential
risk to health, like falls and urinary tract infections.[21] Aging, although a normal aspect of typical
physiology, does incur some manifestations of physiologic derangement that clinicians should learn
to interpret in context.

Review Questions Go to:

Access free multiple choice questions on this topic.

Comment on this article.

References Go to:

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4. Tchkonia T, Kirkland JL. Aging, Cell Senescence, and Chronic Disease: Emerging Therapeutic
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[PubMed]

Copyright © 2022, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution, and
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Bookshelf ID: NBK556106 PMID: 32310566

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