Ageing (Aging): Observations and Solutions (For professionals)

Ageing (Aging): Observations and Solutions (For professionals)

“With advancing age, skin functions deteriorate due to structural and morphologic changes. In particular, changes in skin barrier integrity, immune function, and nervous system occur, resulting in an incresaed prevalence of certain diseases. As the elderly population is rapidly increasing throughout the world, awareness of these diseases and methods to prevent them has become increasing important.

Although the mechanisms of the aging skin are still poorly understood, new data obtained by expression profiling studies and studies of progeroid syndromes illustrate that alterations in DNA repair and stability, mitochondrial function, cell cycle  and apoptosis, extracellular matrix, lipid synthesis, ubiquitin-induced proteolysis and cellular metabolism play important roles.

The physiologic decline of hormones has also been implicated as a major factor in the initiation of aging. This decline, in addition, may reduce tumor suppression and resault in carcinogenesis.

Better understanding of the molecular mechanisms of aging can open new perspectives and strategies in improving our management of these age-associated diseases.

Changes in Ageing (Aging)

On histology:

• thinning of the epidermis: leads to fragility of the skin and delayed wound healing
• diminished mitotic activity of epidermal cells (diminished proliferation): also lead to thinning of the epidermis
• flattening of the rete ridges: leads to increased erosions

• heterogeneity of the distribution of melanocytes: lentigo and liver spots

• decresed dermal thickness and number of fibroblasts
• reduced adnexal structures and hair follicules: delayed wound reepitheliazation
• reduced microvasculature: impaired thermoregulation
• reduced nerve endings: impaired and altered sensation (dysesthesia)

Aging (Ageing) can be:

• intrinsic and is influenced by genetic and cellular factors
• extrinsic and is influenced by Ultraviolet light (UV), tobacco and environmental factors (dioxin, pollution…)

Understanding of aging has been facilited by the observation and study of the progeroid syndromes:

• Rothmund-Thompson Syndrome
• Werner Syndrome (also called adult progeria)

1. mutation of the WRN gene which encodes a helicase
2. helicases are involved in the repair of DNA

• Ataxia Telangiectasia
• Hutchinson-Gilford Syndrome

Ageing on a more molecular level:

• A. intrinsic and extrinsic aging lead to the generation of reactive oxidative species (ROS).

1. ROS constitutes oxidative stress which damages DNA, cell membranes and cell proteins.
2. ROS stimulates MAP kinase, which stimulates AP-1. This in turn stimulates collagenase lesading to collagen destruction
3. MAP kinase alters TGF Beta signaling. This in turn leads to reduced collagen synthesis.
4. ROS increases NfKappaB expression which leads to collagen damage.

• B. Extrinsic aging leads to expression of elastin and subsequent solar elastosis.

What are the solutions ?

• Antioxydants

1. At the food level: Pecans, Mexican Red Beans, Kidney Beans, Walnuts.
2. At the Vitamin Level: Vitamin C, Vitamin E, Carotenoids (Vit A precursors).
3. At the botanical leves: Green Tea (contains polyphenols), Red Wine (Resveratrol which is a polyphenol)

• Caloric Restriction (Delays aging as well as cancers)
• Hormonal Replacement Therapy (HRT) (Delays Aging but increses the risk of cancer). A solution could be to use it topically.
• Topical 5-FU and Imiquimod

Contributors:

Dr Christophe HSU – dermatologist. Geneva, Switzerland

Source: Dr Tey Hong. Come grow old with me – Geriatric Dermatology