Friday, August 31, 2012

The Changes that Occur with Aging in Women

by Dr. Margaret Aranda

Simply put, Age Management Medicine (AMM) is the study of how the human body ages with time.  We do not strive to "reverse" the effects of aging, because well...we are medical doctors and we know the process of aging is something to be respected.  Aging affects DNA on the cellular level, thus virtually every Organ System is affected.


Some of the major Organ Systems and the effects of normal Aging on the woman are listed below:

Vital Signs:  Temperature per se does not change, but the body's ability to compensate to ambient temperature changes.  Elders may wear multiple layers of clothing because redistribution of body fat takes away fat from the subcutaneous tissue.  In hot weather, sweating does not occur readily, so heat intolerance and heat stroke can occur.  Fever, when it occurs, may occur as a single symptom for several days, requiring a healthcare assessment. An inability to mount a febrile response may occur, so the lack of a fever with illness does not rule out a disease process.  Blood Pressure:  Orthostatic hypotension, pre-syncope, and syncope can occur.  Elder women are at risk for hypertension, bradycardia, tachycardia, and arrhythmias such as atrial fibrillation.  Heart rate:  Medications like digitalis or beta-blockers will slow the heart rate.  Respiratory Rate:  Should be normal.

General:  Fatigue, headaches, brain 'fog', mood swings, depression, memory loss, insomnia and sleep deprivation, water retention, and bloating.  To middle age, body fat increases and then eventually decreases.  Changes in the distribution of fat occurs such that fat formation around the abdominal organs occurs preferentially to fat formation under the skin.  "Android fat deposition" leads to increased fat around the abdomen and upper body.  Estrogen dominance can lead to allergies and subsequent manifestations like hives and asthma, as well as autoimmune disorders including Sjoegren's disease.

HEENT:  Head:  Hair thinning, gray hair.  Male-pattern baldness.  Eyes:  Decreased compliance of the lens, decreased ability of lens to thicken, decreased acuity, and the eyes less able to focus on near objects, or presbyopia.  Hence, the need for bifocal glasses.  There is a loss of depth perception, loss of peripheral vision, and a decreased ability to clarify pastel colors.  Decreased number of conjuctival cells, decreased tear production, dry eyes.  Over 60 years old, a benign gray-white ring about the cornea may form, secondary to cholesterol and calcium salts, called arcus senilis.  Macular degeneration or retinal detachment may occur.  Ectropion may occur from weakening of the muscles that close the eye, such that the eye does not closing fully.   Ears:   Increased cartilage and soft tissue mass.  Hair in the ears and decreased hearing acuity.  Decreased ability to distinguish separate sounds when there is background noise.  Nose:  Increased cartilage and nose mass.  Decreased ability to smell.  Airways:  Decreased secretions.  The larynx changes with age, leading to a deeper voice.  The change in pitch can be lower for women, altering the voice so that it is lower.  Cilia no longer move secretions upwards, so there is an increased risk of pulmonary infection when coupled with the decreased cough reflex and the decreased force of cough that also occurs with age.  The nose and airways decrease less IgA, an antibody that fights viruses.  Hence the increased risk of pneumonia.  Sleep apnea, bronchitis, empnysema, and lung cancer may occur.

Cardiac:  In 1995, Olivetti et al compared male and female cardiac tissue in relation to changes of aging.  In the female heart, ventricular muscle mass was unchanged, as were the number of monocytes, average cell volume, and average cell diameter versus their male counterparts.  Males age 17 - 95 had a progressive drop of 1 gm myocardium/year, leading to a final loss of -64,000,000 cells. The remaining cells increased in volume such that the right ventricle increased by 167 μm3  /year, and the left increased by 158 μm3 /year.

Decreased compliance of the ventricles of the heart.  The left ventricular wall may thicken, and the ejection fraction may decrease.  Arteries stiffen and have less compliance, leading to increased blood pressure.  Decrease in the maximum heart rate, valve stiffness, dissecting aneurysm, and heart failure occurs 10 times more commonly in patients over 75 years of age.  Plaque builds up in arterial walls, leading to arteriosclerosis, myocardial infarction, and cerebral vascular accident or stroke.

Respiratory:   Lungs:  Starting at age 20, decreased elasticity due to decreased elastin, decreased production of new alveoli, decreased intercostal muscle size.  At age 30, the rate of air flow through the airways decreases.  Ren et al recently described that the following pulmonary function test parameters decrease with age:  VC, FVC, FEV(1), FEV(1)/FVC, PEF, FEF(25), FEF(50), TLC, and D(L)CO.  In older patients, the airways close more readily, leading to atelectasis that can be profound to the point of causing pneumonia for patients that are bed-bound.  This is why it is important for patients to get out of bed or use incentive spirometry.    Additionally, elders have a decreased cerebral response to both decreased oxygenation and hypercarbia.

Metabolism:   Starting at age 45, muscle mass decreases by 10% per 10 years.   Even with no change in weight, muscle mass decreases and body fat increases.  Muscles burn more calories than fat, so that  there is a need for fewer calories to be consumed.  This change in body composition is primarily responsible for the increased weight seen with aging.  Other reasons include a decrease in calories used by the heart and liver for metabolism.

Decreased metabolism rate for medications and alcohol, requiring decreased dosages as age progresses.  The adverse effects of metabolic changes with oxidative damage involve both cancer and aging.

Urologic:  Bladder:  Increased urinary frequency, decreased size and mass, and decreased efficiency.  (In males, increased prostate gland size may occur.)

Neurologic:   Brain:  Loss of structures for nerve cell connections, decreases in memory, increases in "senior moments".  Slowed reflexes during such things as driving.  There may be a need to increase the length of space between the patient and the car in front of her.  There may be an increased risk of falls, leading to hip fractures, extended hospital stay with surgical repair, rehabilitation, and the possible need for a full-time Caregiver.

Both Vitamin B-12 and folate deficiencies cause depression, memory loss, psychosis, peripheral neuropathy, and personality changes.  Vitamin B-12 deficiency leads to megaloblastosis and degeneration of the dorsal and lateral spinal column, with presenting signs of ataxia, weakness, and loss of proprioception and vibration.  Mental and neurological changes can become permanent without intervention. 

Extremities/Bones:  Cold hands and feet.  Bones:  From about 35 years of age, a decrease in bone replacement occurs, leading to osteopenia and osteoporosis.  Either kyphosis (front-to-back curvature) or scoliosis (side-to-side curvature) may occur.  Muscles:  Decreased muscle mass, especially with no exercise regimen.  Increased atrophy if bed-bound.

Skin:  Decreased skin collagen.  Slowed nail growth, more brittle nails.  Increased dryness, increased wrinkles, and delayed healing.

Endocrine:  Cold intolerance, cold hands, weight gain, menstrual irregularities, hypoglycemia, or hyperglycemia, increased copper, magnesium and zinc deficiency.  Insulin resistance may occur, especially with a high glycemic diet and no exercise.  Propensity toward hypogonadism, hypothyroidism, diabetes, and obesity, with all the sequelae of these diseases.

Elders are 4-5 times more likely to get tuberculosis, cancer, or Herpes Zoster due to decreased Growth Hormone (GH), decreased IGF-1 production, and decreased immune function (Gelato M, 1996).  If one looks at 24 hour GH secreted by a normal-aged patient with an organic pituitary lesion and a diagnosis of hypopituitarism, the laboratory features are indistinguishable from an adult who is over 60 years old (Toogood et al, 1996)

GI:   Increased abdominal girth, less subcutaneous fat, increased fat around the organs, android body habitus, gallbladder disease, and fatty liver.  Atrophic gastritis can occur because the parietal cells progressively diminish in their ability to secrete hydrochloric acid, leading to hypochlorhydria and Vitamin B12 deficiency.

A rare cause of Vitamin B12 deficiency is pernicious anaemia (PA), which is an autoimmune disease affecting perhaps 1-3% of the elderly; its incidence increases with age.  It is virtually unknown to occur until after 50 years of age, and African Americans are more likely to have an earlier age of presentation.   In PA, there is malabsorption of dietary and biliary Vitamin B12.  Usually Vitamin B12 storage lasts 3-5 years, but once PA is diagnosed, storage depletion can occur such that the final stages of deficiency are rapid.  If untreated, this may result in death within months.  Since plants do not synthesize Vitamin B12, a prolonged and strict vegan diet may lead to Vitamin B12 deficiency.

High homocysteine levels (over 20 μmol/L) can be found in the elderly, contributing to increased cardiovascular event and dementia.  The HOPE-2 trial showed that giving folate, Vitamins B6 and B12  reduced the risk of stroke, but there was an increased risk of stroke on the affected side. 

Sexual:  Women go through pre-menopause, menopause, and post-menopause.  Menses become irregular, then eventually stop, causing infertility.  The following hormones change: estrogen, progesterone, and testosterone.   The loss of progesterone influence that occurs with menopause leads to "estrogen dominance".  This occurs whether the estrogen levels are high, moderate, or low;  the key fact is that the effect of progesterone on estrogen is lost.  Hot flashes can occur, as well as decreased libido and dyspareunia.  Decreased vaginal lubrication, atrophy of labia majora and labia minora. Estrogen dominance can lead to irritability and insomnia, increased blood clotting and increased risk of stroke, polycystic ovaries, uterine cancer, uterine fibroids, fibrocystic breasts, and breast cancer.  (In men, decreased sperm production, increased prostate size, decreased testosterone, decreased libido, erectile dysfunction.)

Cellular:   On the Cellular level, a fundamental factor attributed to the aging process is the issue of genetic instability.  The components of DNA damage, DNA repair, DNA longevity, instability of gene expression, and DNA expression with protein interaction, transcription, and mDNA division are involved.  Post-translational oxidation and glycosylation of proteins have been implicated in the accumulation of DNA errors, which may lead to cell death.

Telomere Length:  In 1989, Lundblad and Szostak developed an assay that showed senescence of yeast occurring in relation to a defect in telomere elongation and increased frequency of chromosome loss.  Honig et al have recently described an overview of the association of shorter leukocyte length with mortality and dementia.  More on telemere length later.

As you can imagine, aging takes on a variety of factors that affect not only our bodies, but our minds and souls as well.  We hold that a key in aging successfully means understanding the processes, implementing a plan to avoid adverse outcome, and well, just striving to live life to the fullest.




References:

Carmel, R. Prevalence of undiagnosed pernicious anaemia in the elderly.  Arch. Intern. Med.  156:1097-1100.

Gelato, M.  Aging and immune function: a possible role for growth hormone.  Hormone Research. 1996; 45:46-9.

Honig LS, Kang MS, Schupf N Lee JG, and Mayeux R.  Association of shorter leukocyte telomere repeat length with dementia and mortality.  Arch Neurol Jul 23:11-8. 2012. See Article Here

Janssen, I and Ross R.  Linking age-related changes in skeletal muscle mass and composition with metabolism and disease.  J Nutr Health Aging.  9(6):408-19; 2005.  See Article Here

Lonn, E., et al.  Homocysteine lowering with folic acid and B vitamins in vascular disease. HOPE-2 Trial.   N Engl J Med 354(15):1567-77.

Lundblad V, Szostak JW.  A mutant with a defect in telomere elongation leads to senescence in yeast. Cell; 57(4):633-43; 1989. See Article Here

Olivetti G, et al.  Gender differences and aging: effects on the human heart.  J Am Coll Cardiol. 26(4):1068-1079, 1995.  See Article Here

Prunieras M.  General process of aging.  (Article in French) Rev Fr Gynecol Obstet; 86(6): 421-3; 1991.  See Article Here

Ren, WY, LiL, Ahar RY, and Zhu L.  Age-associated changes in pulmonary function: a comparison of pulmonary function parameters in healthy young adults and the elderly living in Shanghai.  Chin Med J (Engl)  125(17):3064-8; 2012. See Article Here

Toogood AA, et al.  Growth hormone deficiency in adults over the age of 60 years.  J Clinical Endocrinol Metab.  1996;82-460-465.

Wang YT, et al.  An investigation of vitamin B12 deficiency in elderly inpatients in neurology department. Neurosci Bull. Aug 2009;25(4):209-215.


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Other Articles by Dr. Margaret Aranda








2 comments:

  1. Such an interesting blog. I learned a lot. The increase in abdominal size is part of natural aging, yet also can be a sign of ovarian cancer. Women must pay attention to how much and the time frame that abdominal changes occur.
    I believe in the beauty of the human; physically, emotionally/mentally, and spiritually.

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    Replies
    1. You are absolutely right. With ovarian cancer, many times the only presenting symptom is an increase in abdominal girth. It behooves us women to keep that tape measure to our waist. Any increase in waist size may be an ominous sign of advanced ovarian cancer. More research is needed to find a good marker so that we can catch ovarian cancer before it is too late.

      The human body is amazing. Not just the anatomy, but also the physiology and the spirit. When I went to Oral Roberts University Medical School, we learned the focus: mind, body, and spirit.

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