Science of Aging

• Aging

  Progressive physiological changes that lead to senescence, or a decline of biological functions and of the organism's ability to adapt to metabolic stress
• Aging

  • Occurs at the cellular level
  • Reflects both a genetic program and cumulative environmentally imposed damage
• Factors accelerating aging

  • Genetic predisposition
  • Smoking
  • Emotional stress
  • Disease process
  • Exposure to extreme environments e.g. chronic sun exposure
• Compared to a young adult, a geriatric would only have: 92% of brain weight, 85% of basal metabolism, 70% of kidney filtration rate, 43% of maximal breathing capacity, Shortening of telomeres
• Modern biological theories of aging

  • Programmed longevity (switching on and off of some genes)
  • Endocrine factors / hormonal control
  • Immunological theory (immune system decline -> disease vulnerability)
  • Wear & tear theory (the greater the O2 basal metabolism rate, the shorter the lifespan)
  • Cross linking theory (accumulation of cross-linked proteins damages cells and tissues which lead to slowing down of bodily processes)
  • Free radical theory (superoxides / free radical damage)
  • Somatic DNA damage theory (imbalance of DNA damage and repair)
• Aging skin - Epidermis

  • Decrease in skin cell turnover
  • Decreased rate of epidermal repair
  • Increased permeability of skin
• Aging skin - Dermis

  • Decrease in bulk
  • Decrease in fibroblast
  • Loss of collagen
  • Fragmented collagen bundles
  • Reduced elastin fibres
• Aging skin - Changes in Pigmentation

  • Irregular pigmentation
  • Senile lentigines
  • Localized proliferation of melanocytes at the dermal-epidermal junction
  • Greying of hair
  • Bulbs of hair – lack or deficient in Tyrosinase
  • Decrease of melanocytes
• Aging skin - Hair follicles

  • Density of hair follicles are reduced
  • Shortening of anagen phase
  • Thinning of hair
• Aging skin - Nail growth

  • Decrease in nail growth
  • Thickened fingernails and toenails
• Aging skin - Sebaceous and Apocrine glands

  • Decrease in sebum, Apocrine glands regress with age
• Aging skin - Eccrine glands

  • Reduction in number and output
• Aging skin - Nerves and sensation

  • Decreased sensory perception, increased threshold for pain
• Aging skin - Immune functions

  • Reduced Langerhan's cells, T cells, increased autoantibody
• Menopause

  • Reduction in follicles
  • Atrophy of ovaries
  • Decrease in oestrogen
  • Smaller uterus and shorter vagina
  • Glandular tissue of breast replaced by fibrous tissue
  • Loss of elasticity in the pelvic supporting ligaments
• Actinic damaged skin

  • Presence of thickened, degraded elastic fibres
  • Increased gylcosaminoglycals and proteoglycans
  • Decrease in matured collagen
• Facial aging - Process of Atrophy

  • Aging process is largely manifested with gravity inducing inferior vector of ptosis
  • Progressive disruption of dermal connective tissue layer including the elastic fibers that maintain the physiologic recoil and laxity of the skin
  • Ratio of Type I: Type III collagen becomes reduced - (normal 6:1)
• Facial fat compartments

  • Infraorbital fat (IF)
  • Superficial medial cheek fat (SMCF)
  • Nasolabial fat (NLF)
  • Middle cheek fat (MCF)
  • Lateral temporal-cheek fat (LTCF)
  • Superior Jowl fat (SJF)
  • Inferior Jowl fat (IJF)
  • Medial Suborbicularis Oculi Fat (M-SOOF)
  • Lateral Suborbicularis Oculi fat (L-SOOF)
  • Deep medial cheek fat (DMCF)
  • Buccal fat (BF)
• V frame deformity

  • Medial Suborbicularis Oculi Fat (M-SOOF)
  • Lateral Suborbicularis Oculi Fat (L-SOOF)
  • Deep medial cheek fat (DMCF)
• Changes in the aging face

  • Photoaging manifests as fine lines, rhytides, and laxity
  • Fat loss manifests as infraorbital hollows, nasolabial folds, and jowling
  • Bone resorption and remodelling of maxillary bones
  • Alveolar ridge and mandibular resorption
  • Widening of the orbital socket

  
• The anchoring complex

  • Dermis
  • Retinacular cutis (skin tendons)
  • SMAS
  • Retaining Ligament
  • Periosteum
• Weakening of the anchoring complex with aging

  • Overall ptosis of the soft tissues
• Facial muscle aging

  • Loss of muscle tone
  • Changing of dynamics between muscle groups
  • Loss of muscle support by underlying structures
  • Anchoring complex weakening
• Basement membrane of the skin

  • Highly specialized ECM composed of distinct glycoproteins & proteoglycans
  • Structural support to keratinocytes
  • Participating in epidermal renewal
  • Taking part in repair processes during skin healing
  • Adhesive scaffold
  • Function as signaling platforms by sequestering growth factors and other ligands (cell to cell communication)
  • Regulates molecular movements and diffusions
  • Allows exchange of nutrients / fluids between the epidermal-dermal layers (epidermal-dermal interaction & signaling)
• Regions of basement membrane zone

  • Hemidesmosomes (connecting epidermis)
  • Lamina lucida composed of laminins
  • Lamina densa 35–45 nm thick electron dense layer composed mainly of type IV collagen, perlecan (heparan sulfate proteoglycan), and possibly laminin
  • Sub-lamina densa fibrillar structures connecting lamina densa to anchoring fibrils
• Basement membrane alterations with aging

  • Flattening of BM is seen both in sun-protected & sun-exposed skin of the elderly
  • In younger individuals, photoaged skin shows much more prominent flattening of BM than sun-protected sites
  • Epidermal and/or dermal cell derived MMPs damage the BM in photoaging, and the protective effects of MMP inhibitors have been documented
  • Strengthening the BM, enhancing production of laminins and collagens IV & VII, can improve overall integrity of skin, stimulate cell-to-cell communication, epidermal-dermal interactions and signaling; all of which have positive implication
• Hemidesmosomes

  Connecting epidermis
• Lamina lucida

  Composed of laminins
• Lamina densa

  35–45 nm thick electron dense layer composed mainly of type IV collagen, perlecan (heparan sulfate proteoglycan), and possibly laminin
• Sub-lamina densa

  Fibrillar structures connecting lamina densa to anchoring fibrils
• Epidermal and/or dermal cell derived MMPs damage the BM in photoaging, and the protective effects of MMP inhibitors have been documented
• Strengthening the BM, enhancing production of laminins and collagens IV & VII, can improve overall integrity of skin, stimulate cell-to-cell communication, epidermal-dermal interactions and signaling; all of which have positive implications for anti-aging strategies
• After pulsed-RF treatment for melasma, age-related pigmentation, senescent fibroblasts that stimulates melanogenesis were reduced, resulting in improved pigmentation
• Pigmentation was improved by improving SDF1 deficiency and excessive senescent fibroblasts that stimulate melanogenesis after pulsed- RF treatment for senile lentigo
• The expression of the SDF1 mRNA was small in senescent fibroblasts, but more in normal fibroblasts
• The p16INK4A-positive cells appeared more in the lesion than in the perilesional area, and more in the upper dermis than in the lower dermis
• The senescent fibroblasts, which stimulate melanogenesis, are more distributed in the melasma lesion than in the perilesional area, and more in the papillary dermis than in the reticular dermis
• Retinacular cutis (skin tendons)

  • Part of the dermis
• SMAS

  • Part of the dermis
• Retaining Ligament

  • Part of the dermis