Aging

• Growth


  • Physical maturation resulting in increase in size of body and organs
  • Multiplication of cells
  • Quantitative
  • Stops when maturity attained
  • Cellular
• Development


  • Functional and physiological maturation of individual
  • Maturation of CNS including psychological, social and emotional changes
  • Qualitative
  • Occurs throughout life/ progressive increase in skill and capacity to function
  • Organizational and sequence is the same
• Developmental age-periods


  • Infancy
  • Neonate –birth to 1 month
  • Infant- 1 month-1 year
  • Early childhood
  • Toddler – 1 year to 3 years
  • Preschool- 3 years- 6 years
  • Middle childhood
  • School age 6-12 years
  • Late childhood
  • Adolescent 13-18 years
• Aging


  Multifactorial process, characterized by the progressive degeneration of organ systems and tissues
• Primary aging


  Intrinsic changes occurring with age, unrelated to disease or environmental influences
• Secondary aging


  Change due to the interaction of primary aging with environmental influences or disease processes
• Chronological age


  Number of years you've been alive
• Biological age


  How old body cells and tissues are based on physiological evidence
• Factors determining biological age

  • Genetic
  • Environmental- diet, pollutants, radiations, micro-organisms
  • Gender- female >men ; 7-10 years
  • Experiences- education, behaviors- longevity
  • Smoking/stress- increase biological age
  • Exercise- lower biological age
• Life expectancy


  Average number of years that a person can be expected to live
• Male life expectancy 63.7, female 68.4 and total life expectancy is 66.1 (WHO 2020). Average world wide 73.3
• Mutation-accumulation mechanism


  Deleterious mutations in gametes will result in progeny that are defective during most of life, and natural selection removes such genes from the population. A few mutated genes will not have deleterious effects until advanced ages, and natural selection would fail to eliminate such genes
• Disposable soma theory


  Energy balance between reproduction(more) and somatic body maintenance(less) by natural selection- primary role to produce progeny
• Physiologic categories of aging

  • Change in cellular homeostatic functions- Temp, blood volume
  • Decrease in body mass
  • Decline and loss of functional reserve of body. This alters body response to stressors such as trauma, surgery
• WHO classification of aging

  • Developed countries- ≥65 years
  • Developing countries ≥60 years
• Gerontologists' classification of aging

  • Young-Old = (ages 65 - 74)
  • Middle-Old = (ages 75 - 84)
  • Old-Old = (age 85 and older)
• Theories of aging


  • Endocrine theory
  • Wear and tear
  • Free radicals
  • Genetic –DNA damage(radiations)
  • Cross linking /glycation hypothesis of ageing
  • Immune
  • Mitochondrial theory of aging-ROS , Mitochondrial DNA- low ATP, histones
• Wear and tear theory

  Cells wear out through exposure to internal stressors, including: - trauma, - chemicals, and - buildup of natural wastes
• Endocrine theory


  Hypothalamus and pituitary are responsible for changes in hormone production. Become less efficient
• Free radicals theory


  Oxidation of organic materials such as carbohydrates and proteins
• Apoptosis theory


  Cells undergo programmed after given number of cell divisions; due to somatic mutations, genetic errors
• Immune theory


  Decrease in immune function leads to increase in autoimmune responses
• Cross linking theory


  Irreversible aging of proteins is responsible for the ultimate failure of tissue and organs. Protein molecules binds one another by means of glucose molecule- a process known as glycation-amadori products. Repair enzymes of the cell can not break those bonds. An accumulation of cross-linked proteins damages cells and tissues, slowing down bodily processes resulting in aging
• Cellular and molecular mechanisms of aging

  • Oxidative stress
  • Inadequate repair of damage
  • Dysregulated cell number
• Dysfunction of the homeostasis of cell number

  • Telomeres and Hayflick limit- germline and cancer cells
  • Inability to proliferate t cells- Shorter telomeres
  • Apoptosis – dysregulated apoptosis cause aging
  • Death receptors
  • Mitochondrial
  • Damage to nuclear DNA –BAX/BCL-2 imbalance. Role of p53 and p21
• Inadequacy of repair processes

  • DNA repair theory of aging proposes that DNA repair declines with advancing age. Severe DNA damage stimulate the P53 to increase the synthesis of proapoptotic molecules
  • Decrease in chaperone proteins—involved in protein folding and refolding leads to accumulation of protein oligomers and aggregates which are toxic- alzheimers disease
  • The ubiquitin/proteasome system catalytic activity decreases with age
  • Autophagy – macroautophagy (vesicles), microautophagy and chaperone mediated autophagy. Lysosomes undergo changes
• Oxidative stress


  • Metabolism –ROS ( hydroxyl, superoxide , hydrogen peroxide) damages proteins, lipids, and DNA
  • Role of thyroid hormone synthesis
  • Destruction of certain bacteria (NADPH) oxidase and myeloperoxidase in phagocytic cells
  • Imbalance between the production and removal of ROS by antioxidant defenses is the major cause of aging
  • Glycation - nonenzymatic reactions between reducing sugars and the amino groups of macromolecules (e.g., proteins, DNA) to form advanced glycation end products (AGEs).- role in diabetes, lens opacification, collagen stiffness e.g blood vessels. , DNA damage
  • Mitochondrial DNA damage- lack histone proteins. Less ATP, aging
  • DNA damage- ROS, radiations. Interfere with transcription and cell cycle
• Physiological effects of aging

  • Central nervous system – sensory
  • Motor and cognitive
  • Cardiovascular system
  • Pulmonary system
  • Exercise
  • Endocrine system
  • Skeletal muscle
  • Urinary system
  • Skin
  • Bones
  • GIT
  • Height and body composition
• Central nervous system – sensory effects of aging


  • Reduce sensitivity to perception- touch, vibration, 2point vibration, proprioception
  • Thermoregulatory dysfunction- inability to sense cold and heat
  • Hearing loss esp high frequency- loss of hair cells, auditory nerves, low blood supply to cochlear, deficit in central processing
  • Loss of vision- loss of accommodation/ presbyopia; reduced number of cones, altered pupillary light reflex and darkness, reduced number of cones; diseases- glaucoma, cataract, macula degerations
  • Reduction in taste and olfaction
• Motor and cognitive effects of aging

  • Slow reaction time –slowing of central processing
  • Inability to maintain posture and balance- slow central processing, reduced vision, proprioception and muscle strength
  • Cognitive decline (memory, intelligence and learning) is not marked in the absence of dementia
  • Older people can learn but at a slower pace
• Cardiovascular effects of aging

  • Aging decreases the distensibility of arteries- decreases compliance
  • Elevates systolic pressure, slightly decreases diastolic pressure, and thus widens pulse pressure
  • Afterload increases due to reduced compliance. This leads to compensatory thickening of left ventricular wall (size not number)
  • End diastolic volume(preload) does not change- increase in active filling phase and decline in early diastolic filling
  • Postural hypotension due to blunted arterial baroreceptor reflex
• Pulmonary effects of aging

  • Strength and endurance of the respiratory muscles decrease with age, primarily because of atrophy of type IIa muscle fibers
  • Lung volumes—both static volumes and forced expiratory volumes gradually decrease with age
  • Atelectasis of small airways- degeneration of collagen/ elastic tissue
  • Impaired ventilation of dependent lung regions, ventilation-perfusion mismatch, and reduced resting arterial partial pressure of oxygen
  • Healthy elderly people do not experience a failure of either ventilation or gas exchange, affected during ill-health
• Exercise effects of aging

  • Decrease in oxygen uptake by tissues – low CV and pulmonary fnx
  • Stroke volume increase more , while HR increases modesty
  • Left ventricular end-diastolic and end-systolic volumes increase, and maximal left ventricular ejection fraction falls
  • Decrease in the pulmonary diffusing capacity (DL )—due in part to decreased alveolar capillary volume. V/Q mismatch
  • Skeletal muscle and the cardiovascular system remain responsive to exercise into the 10th decade of life
• Endocrine effects of aging

  • Decrease in resting metabolic rate
  • Impaired glucose tolerance- insulin resistance due to increased adiposity and reduced physical activity
  • Decrease in insulin secretion/ GH and IGF-1
  • Modest increase in secretion of cortisol/ preserved aldosterone
  • Reduction of dehydroepiandrosterone levels
  • Thyroid hormone unaffected until 9th decade. TSH levels thereafter decreases and T3 due to impaired 5 and 3 prime deiodinase
  • Menopause at 50 years
  • Progressive decline in male reproductive functions- andropause
  • Plasma parathyroid hormone levels increase
• Skeletal muscle effects of aging

  • A steady loss in skeletal muscle mass—sarcopenia. >50 years. This is due to inactivity and progressive loss of the motor neurons innervating type II motor units
  • Affected muscle fibers either atrophy and die or become innervated by a sprout that emerges from a healthy axon nearby. This process of reinnervation ultimately results in larger motor units and thus a decrement in fine motor control
  • The reduction in muscle strength and power
  • Joint flexibility falls, due mainly to thinning of cartilage, decreased tensile stiffness, fatigue resistance, and strength due to reduced water content
  • Increased cross-linking of collagen due to impaired chondrocytes
• Urinary effects of aging

  • Renal blood flow decreases progressively
  • Renin and angiotensin II are lower in older adults
  • Impaired ability to excrete potassium, phosphate, and acid
  • Renal-tubule transport functions decrease with age
  • Bladder symptoms such as urgency, nocturia, and frequency- capacity and compliance of bladder decreases, inappropriate detrusor contractions increases
  • Decreased rate of bladder emptying as well as an increase in residual bladder volume(BPH) due to inappropriate detrusor contractions
• Skin effects of aging

  • In intrinsic aging, the thickness of the epidermis decreases slightly, with no change in the stratum corneum
  • Reduce rate of generation of keratinocytes
  • Reduce photoprotection- low melanocytes; casing gray hair on hair follicle
  • Reduce immunity- low Langerhans cells
  • Dermis- elastin and collagen decreases. It thins by ~20% and becomes stiffer, and more vulnerable to injury
  • Nail growth also slows with increasing age
  • Number and function of sweat glands decreases, sebum
• Bone effects of aging

  • Remodeling of bone occurs throughout adult life
  • Slow progressive loss in bone mass in 3rd decade due to decreased insulin-like growth factor 1 (IGF-1), and increased parathyroid hormone
  • Low levels of estrogen and testosterone are also involved at advanced ages
• GIT effects of aging

  • Loss of ability to secrete gastric acid
  • Age-related decreases in function (i.e., chewing, swallowing, fecal continence) due to loss of skeletal muscle
  • Liver mass and hepatic blood flow
• Height and body composition effects of aging

  • Peak height- males 18 to 19 years; females 16 to 17 years
  • Height starts to decline @20 women; 25 men- compression of the cartilaginous disks between the vertebrae and loss of vertebral bone
  • Body mass increase until middle age and start to decline at 70 years
  • Both fat-free mass and lean body mass progressively decrease over most of adult life in both sexes
  • Adipose-tissue fat mass increases with adult age
  • Accumulation of fat around abdominal viscera and in abdominal subcutaneous tissue
  • Decrease in fat occurs in the extremities and the face-gaunt face
  • Visceral adipose tissue is an important source adipokines that promote inflammation, which aids the occurrence and progression of senescence