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What’s Important?

  1. There is much overlap between intrinsic and extrinsic aging.

  2. Keratinocyte and fibroblast functions change with aging.

  3. Senescent cells develop a secretory phenotype that accelerates aging.

What’s New?

  1. Emerging research is demonstrating the importance of the “tissue skeleton,” consisting of fibroblasts and their attachments to the ECM molecules.

  2. Lipofuscin contributes to skin aging by reducing the activity of the proteasome.

  3. Autophagy decreases the rate of aging. Mitochondrial autophagy is especially important.

What’s Coming?

  1. Research evaluating the effects of mechanoforces between fibroblasts and the ECM and ascertaining how these change with age.

  2. Understanding the changes in mechanoforces and how they affect genetic expression and fibroblast function.

  3. Identifying epigenetic methylation patterns of aged skin.

  4. Controlling macroautophagy of mitochondria may be an anti-aging strategy in the future.

  5. Timely clearance of senescent cells before they create too much damage may be an approach to prevent skin aging.

There are two main causes of skin aging, intrinsic and extrinsic. The extrinsic causes can be decreased by changing lifestyle habits (see Chapter 6, Extrinsic Aging). Intrinsic aging is caused by internal cellular processes that occur due to daily metabolism and normal cellular processes. The etiology of intrinsic aging can be influenced with diet, exercise, oral supplements, topical treatments, and lifestyle habits but cannot be completely eliminated. There is much overlap between intrinsic and extrinsic aging. This chapter will discuss cellular processes and hormonal changes that affect the skin in the absence of sun and pollution exposure.1 However, for a more complete explanation of aging, please consider this material and Chapter 6 in tandem, because some of the issues discussed in the extrinsic aging chapter apply here as well.


Intrinsically aged skin is smooth, finely wrinkled, thinner, more fragile, and less elastic than younger skin. Intrinsically aged skin is seen in body areas not exposed to the sun and does not exhibit solar lentigos and other pigmentation changes associated with sun exposure. Although studies compare data from sun-exposed areas to those not exposed to the sun to elucidate the effects of intrinsic and extrinsic aging, there is much overlap because all skin withstands some sort of environmental exposure. However, there are characteristics unique to sun-protected aged skin.

Changes to the Epidermis

Keratinocytes are dynamic and change between phenotypes that display stemness, proliferation, differentiation, and senescence. The epidermis is a self-renewing tissue that relies upon the keratinocytes that exhibit stemness (i.e., that function as stem cells) to repopulate the epidermal layers. As aged keratinocytes display less stemness, the epidermis becomes thinner and develops flattening of the rete pattern. Young keratinocytes that have a high self-renewal capacity in vitro exhibit a high level of the epidermal stem cell marker β1 integrin, while older keratinocytes express much less of this stem cell marker. Keratinocytes that demonstrate stemness do not divide ...

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