Several theories may explain the normal aging process, either alone or in combination
with other theories (Table 1). These theories can be generally classified into evolutionary, involving historical
and evolutionary aspects of aging, and physiologic or structural and functional changes.
Processes that may explain these theories at a cellular level include intrinsic timing
mechanisms and signals, accidental chance events, programmed genetic signals making
an organism more susceptible to accidental events, nuclear or mitochondrial DNA mutations
or damage, damaged and abnormal proteins, cross-linkage, glycation, waste accumulation,
general molecular wear and tear, free radical formation, and specific cellular components
such as gene, chromosome, mitochondria, or telomeres. Physiologic processes that may
explain aging include oxidative stress, immunologic, neuroendocrinologic, metabolic,
and insulin signaling, and caloric restriction.
1
Table 1Major cellular and functional changes of aging by prominent theories and major associated
clinical disease outcomes
| Organ System | Major Theories | Cell Level | Structural/Functional Changes of Aging | Disease Outcomes |
|---|---|---|---|---|
| Integumentary | Oxidative stress; free radical; genetic; autoimmune | Melanocytes, mast, and Langerhans cells | Thinning of stratum corneum and subcutaneous layer | Squamous and basal cell carcinoma; malignant melanoma |
| Oral | Oxidative Stress; free radical; genetic; autoimmune | Buccal | Increased thickness of tooth dentin, decreased dental pulp; thinning of oral mucosa and receding of gums; decreased sensitivity for smell and taste | Squamous cell carcinoma; tooth decay |
| Visual | Oxidative stress; free radical; genetic | Rods and cones | Reduced night vision, accommodative ability and increased glare | Macular degeneration; cataracts; diabetic retinopathy |
| Hearing | Oxidative stress; free radical; genetic | Sensory and neural cells | Stiffening of the inner ear bones | Presbycusis; osteosclerosis |
| Musculoskeletal | Oxidative stress; genetic; autoimmune | Myocytes | Apoptosis, reduced size of myofibrils, decreased type 2 muscle fibers; decreased hand grip strength with more in the lower extremities | Falls; disuse atrophy; chronic musculoskeletal disorders |
| Skeletal | Oxidative stress; free radical; neuro endocrine | Osteoblasts and osteoclasts | Change in bone architecture and accumulation of microfractures, disparity in the concentration of deposited minerals, changes in the crystalline properties of mineral deposits and protein content of the matrix; decreased height and thinning of bone | Fractures |
| Cardiovascular | Oxidative stress; free radical; neuroendocrine; genetic | Myocyte; pacemaker cell | Increase in left ventricular stiffness and decrease in compliance; decreased left ventricular diastolic filling and relaxation, increased stroke volume, reduction in maximal cardiac output and vasodilator response to exercise | Congestive heart failure; cardiomyopathy; heart block |
| Pulmonary | Oxidative stress; free radical; genetic; autoimmune | Alveolar cells | Chest wall stiffness; decreased arterial oxygenation and impaired carbon dioxide elimination; decrease in vital capacity and forced expiratory volume, increased residual volume and functional residual capacity | Chronic lung disease; carcinoma |
| Gastrointestinal | Oxidative stress; free radical | Mucosal cell | Decreased elasticity of connective tissue; reduction in phase I metabolism | Carcinoma; increased risk of drug–drug and drug–disease interactions |
| Renal/urogenital | Oxidative stress; free radical; genetic; neuroendocrine; autoimmune | Renal cell | Diminished proliferative reserve; apoptosis; loss of glomerular and tubular mass; decline in GFR, loss of tubular volume and narrowed homeostatic control of water and electrolyte balance | Carcinoma; chronic renal failure |
| Neurologic | Oxidative stress; free radical; genetic; neuroendocrine | Neurons; glial cells | Decrease in size of hippocampus and frontal and temporal lobes; decreased number of receptors of all types in the brain with increased sensitivity; decrease in complex visuoconstructive skills and logical analysis skills; decrease in processing speed, decrease in reaction time and decrease ability to shift cognitive sets rapidly; memory distraction and decline in executive function; abnormal reflexes | Neuropathy; neurodegenerative disorders |
| Hematologic | Autoimmune; genetic; oxidative stress; free radical | Stem cells | Decreased marrow cellularity, increase in bone marrow fat and reduction in cancellous bone | Chronic anemia; myelofibrosis; leukemia |
| Neuroendocrine | Neuroendocrine; oxidative stress; genetic | Neuroendocrine cells; mitochondria | Decrease or increase in hormone levels; inability to conserve or dissipate heat | Autonomic neuropathy; thyroid disease; adrenal insufficiency; male and female menopause |
Keywords
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References
- Geriatric review syllabus: a core curriculum in geriatric medicine.in: 7th edition. American Geriatrics Society, New York2010: 9-14
- Analysis of Aging-related oxidative stress status in normal aging animals and development of anti-aging interventions.Yakugaku Zasshi. 2010; 130: 29-42
- Background ionizing radiation plays a minor role in the production of chromosome translocations in a control population.Int J Radiat Biol. 1999; 75: 819-827
- Can normal aging be explained by the immunologic theory.Geriatrics. 1997; 32: 111-116
- Invited review: theories of aging.J Appl Physiol. 2003; 95: 1706-1716
- Longevity and heredity in humans.Ann N Y Acad Sci. 1991; 621: 78-89
- Anti-inflammatory mechanisms of dietary restriction in slowing aging processes.Interdiscip Top Gerontol. 2007; 35: 83-97
- Telomeres, telomerase, and human disease.N Engl J Med. 2006; 355: 1195-1197
- Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span.Curr Biol. 1998; 8: 279-282
- The physiology of aging.in: Dharmarajan T.S. Norman R.A. Clinical geriatrics. The Parthenon Publishing Group, Boca Raton (FL)2003: 9-22
- Upright standing and gait: are there changes in atttentional requirements related to normal aging?.Exp Aging Res. 1996; 22: 185-198
- Gait Instability and fractal dynamics of older adults with a “cautious” gait: why do certain older adults walk fearfully?.Gait Posture. 2005; 21: 178-185
- Common dermatological conditions in aging.in: Rosenthal T. Naughton B. Williams M. Office care geriatrics. Lippincott Williams & Wilkins, Philadelphia2006: 491-492
- Geriatric review syllabus: a core curriculum in geriatric medicine.in: 7th edition. American Geriatrics Society, New York2010: 390-391
- Normal aging.in: Harm R.J. Sloane P.D. Warshaw G.A. Primary care geriatrics. 5th edition. Mosby, Louis2002: 23-24
- Visuomotor adaptation in normal aging.Learn Mem. 2003; 10: 55-63
- Molecular mechanisms of cell death in the ear.Ann N Y Acad Sci. 1999; 884: 41-51
- Aging and hearing.Hear Res. 2010; 264: 1-2
- Liberalization of the diet prescription improves quality of life for older adults in long-term care.J Am Diet Assoc. 2005; 105: 1955-1965
- Skeletal muscle aging: role of reactive oxygen species.Crit Care Med. 2009; 37: S368-S371
- Involvement of oxidative stress and caspase 2-mediated intrinsic pathway signaling in age-related increase in muscle cell apoptosis in mice.Apoptosis. 2008; 13: 822-832
- Modeling normal aging bone loss, with consideration of bone loss in osteoporosis.Toxicol Sci. 2000; 55: 171-188
- Age-related bone changes.Exp Gerontol. 1991; 26: 171-187
- Vertebral structure and strength in vivo and in vitro.Calcif Tissue Int. 1993; 53: S121-S125
- Age-related changes in articular cartilage proteoglycans: electron microscopic studies.J Orthop Res. 1985; 3: 251-257
- Shared phenotypes among segmental progeroid syndromes suggest underling pathways of aging.J Gerontol A Biol Sci Med Sci. 2005; 60: 10-20
- Clinical implications of physiological changes in the aging heart.Drugs Aging. 2001; 18: 263-276
- Effects of aging on cardiovascular responses to parasympathetic withdrawal.J Am Coll Cardiol. 2003; 41: 2077-2083
- Osler maneuver to detect pseudohypertension.JAMA. 1999; 282: 943
- Aging and postural hypotension.J Am Geriatr Soc. 1989; 37: 129-137
- Comparison of diaphragm strength between healthy adult elderly and young men.Am J Respir Crit Care Med. 1995; 152: 677-682
- Effects of aging on respiratory system physiology and immunology.Clin Intervent Aging. 2006; 1: 253-260
- Accelerated lung aging: a novel pathogenic mechanism of chronic obstructive pulmonary disease.Biochem Soc Trans. 2009; 37: 819-823
- Changes in gastrointestinal, pancreatic, biliary, and hepatic function with aging.Gastroenterol Clin North Am. 1990; 19: 227-234
- Clinical pharmacology.in: Burke M. Laramie J.A. Primary care of the older adult: a multidisciplinary approach. 2nd edition. Mosby, Louis2004: 91-154
- The impact of aging on kidney repair.Am J Physiol Renal Physiol. 2008; 294: F1265-F1272
- Effects of aging on kidney function and implications for medical practice.Presse Med. 2000; 29: 1373-1378
- The aging kidney.Geriatrics. 2000; 55: 26-28
- Role of oxidants, inflammation in declining renal function in chronic kidney disease and normal aging.Kidney Int Suppl. 2009; 114: S3-S11
- Urinary incontinence.in: Ham R.J. Sloan P.J. Warshaw G. Primary care geriatrics. 5th edition. Mosby/Elsevier, New York2007: 306-323
- The role of oxidative stress in the pathogenesis of Alzheimer's disease.Bratislavske Lekarske Listy. 2006; 107: 384-394
- Free radical induced oxidative damage in DNA: relation to brain aging and neurological disorders.Indian J Biochem Biophys. 2009; 46: 9-15
- Alzheimer's disease and other dementias.American Psychiatric Publishing, Inc., Washington (DC)2009
- Comprehensive textbook of geriatric psychiatry.3rd edition. WW Norton and Co, New York2004
- Sleep complaints in community-living older persons: a multifactorial geriatric syndrome.J Am Geriatr Soc. 2007; 55: 1853-1866
- Protein homeostasis and aging: taking care of proteins from the cradle to the grave.J Gerontol A Biol Sci Med Sci. 2009; 64: 167-170
- Proteasome inhibition alters neural mitochondrial homeostasis and mitochondria turnover.J Biol Chem. 2004; 279: 20699-20707
- Impact of aging on stress-responsive neuro endocrine systems.Mech Ageing Dev. 2001; 122: 963-983
- Aberrant insulin receptor signaling and amino acid homeostasis as a major cause of oxidative stress in aging.Antiox Redox Signal. 2008; 10: 661-678
- Effects of age, smoking and vitamins on plasma DHEAS levels: a cross-sectional study in men.J Clin Endocrinol Metab. 1992; 74: 139-143
- Pediatric and geriatric hematology.in: Hematology: clinical principles and applications. 3rd edition. Elsevier, St. Louis2007: 531
- The role of stem cells in aging.Exp Hematol. 2003; 31: 659-672
- Estimation of glomerular filtration rate in persons aged 68 years or older: agreement between distinct calculation methods.Rev Esp Geriatr Gerontol. 2010; 45: 86-88
- Clinical guide to prevention and treatment of osteoporosis.(Accessed July 7, 2011)
- New approach to gerontology: building up “successful aging” conditions.Aging Clin Exp Res. 2007; 19: 160-164
- Clinical practice guidelines.(Accessed July 7, 2011.)
- Living healthier for longer: comparative effects of three heart healthy behaviors on life expectancy with and without cardiovascular disease.BMC Public Health. 2009; 9: 487
- The aging process and potential interventions to extend life expectancy.Clin Intervent Aging. 2007; 2: 401-412
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Published online: September 23, 2011
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