What Are The Causes of Aging Skin?

The Science and Causes of Skin Aging

What is the cause of aging skin? Skin aging, characterized by wrinkles, sagging, and thin skin has many causes.  Antiaging skin care ingredients target these specific processes that make skin old.  The causes of skin aging are often divided into intrinsic and extrinsic causes.  This guide to the major causes of skin aging will discuss the science of what makes skin look old. 

This guide to the aging process will continuously be updated as new discoveries about skin aging are made. For more detailed explanation about skin aging see Chapters 5 and 6 of the latest edition of my textbook Baumann’s Cosmetic Dermatology (McGraw Hill 2022).

Biologic Causes of Skin Aging

To protect your skin from the causes of skin aging, you have many skin care product options.  You should choose antiaging skin care based on your Baumann Skin Type.

 Skin Aging Science

Senescent cells cause skin aging. Skin cells (keratinocytes and fibroblasts) go through five different cell phases:

  • Stem cells
  • Proliferating cells
  • Differentiated cells
  • Senescent cells
  • Apoptotic cells

Cellular Senescence and Autophagy and Their Role in Wrinkled Skin

Apoptotic cells are "dead skin cells" and are not viable. They are are eliminated by autophagy and other processes that recycle cellular components. That is why apoptotic cells are not believed to be harmful to the skin.

 However, the more senescent cells you have, the more likely your skin is to wrinkle and age.

Senescent cells have lost the ability to proliferate and lysosomes and mitochondria lose functionality and lose the ability for autophagy.(5)  Senescent cells are not eliminated from the skin, and they stay and causes skin aging.

The presence of senescence cells is associated with an increased rate of aging . The goal of rejuvenating skin is to reduce the number of senescence cells by increasing autophagy.

Senescent cells develop into the senescence-associated secretory phenotype (SASP) which is believed to be one of the major causes of skin aging.

SASP cells cause damage and aging by releasing:

  • proinflammatory cytokines
  • matrix metalloproteinases (MMPs)
  • growth factors
  • chemokines
  • matrix-modeling enzymes
  • lipids,
  • free radicals (7,8) and extracellular vesicles (EVs).

Release of these substances by senescent cells causes inflammation, known as “inflammaging (9)”. This inflammation causes many problems such as loss of collagen, elastin and extracellular matrix (ECM) which leads to fibroblast compaction, reduced DNA synthesis, and eventually wrinkles, fragile skin and thin skin.

Autophagy is the important process in which organelles such as lysosomes and mitochondria(6) self-digest or “eat themselves”.    Autophagy eliminates problem causing organelles and cells like damaged mitochondria, damaged lysosomes and senescent cells.

Sirtuins and Skin Aging

Activation of sirtuin (SIRT-1) has been shown to extend the lifespan in mammals. Caloric restriction (10) also activates sirtuin which is why intermittent fasting has become an antiaging strategy.   SIRT-1 decreases senescence and activates autophagy. 

SIRT-1 chart for skincare

How Do Free Radicals Cause Skin Aging?

ways free radicals age skin

Free radicals (1), also known as reactive oxygen species (ROS), are formed when oxygen molecules lose an electron and are left with an odd number of electrons. An oxygen molecule with paired electrons is stable; however, oxygen with an unpaired electron is “reactive” because it seeks and seizes electrons from vital components leaving them damaged.(2)

What causes free radicals to occur?

Free radicals are formed by:

  • damaged mitochondria
  • inflammation
  • normal cell metabolism
  • pollution
  • smoking
  • ultraviolet light

Normal cellular metabolism can result in free radical formation.  Damaged mitochondria generate free radicals which is one reason why it is so important to protect your mitochondria with antioxidants.

Free radicals attack DNA, cellular proteins, and cellular membranes and steal electrons leaving these cellular components damaged. This can cause inflammation.

Free radicals increase amounts of:

  • inflammatory factors
  • transcription factors, such as activator protein (AP)-1
  • nuclear factor-κB (NF-κB)(3)
  • matrix metalloproteinases (MMPs) such as collagenase, which degrades skin collagen.(4)

how free radicals decrease collagen production

Destructive Enzymes and Skin Aging

Groups of destructive enzymes that cause aging are called matrix metalloproteinases or MMPs.  MMPs are turned on by genes, inflammation and exposure to ultraviolet light and pollution.

Examples of destructive enzymes that cause skin aging are:

  • Collagenase breaks down collagen,
  • Elastase breaks down elastin
  • Hyaluronidase breaks down hyaluronic acid.  

different enzymes that age skin

 

Short Telomeres and Skin Aging

Telomeres are composed of small pieces of repetitive DNA sequences at the ends of chromosomes.  These control the cell cycle. Each cell division shortens the telomere.

 Telomere shortening may cause aging by triggering cellular senescence,(13)   however, the role of telomere shortening in senescence is unclear.

Why are telomeres short? These are believed to play a role in telomere shortening:

  • free radicals,
  • physiologic stress,
  • inflammation
  • other factors

Genes That Cause Skin Aging and Wrinkles

Research is shedding light on which genes are important in skin appearance and function, but it is still many years too early to develop skin care products targeted to “genetic deficiencies”. Glass et al(14) showed that gene studies on aging must be done in human skin to be relevant. Genetic studies on animals and cell cultures do not tell us what we need to know about human genes that cause aging.

Aged skin has increased expression of inflammation-related genes, cytokines and proteases.

Genes that cause skin aging are involved in;

  • cellular metabolism
  • DNA transcription
  • signal transduction
  • cell cycle regulation (15)
  • epidermal differentiation,
  • keratin filaments
  • cornified envelope proteins
  • lipid biosynthesis (16)
  • skin barrier integrity (17)
  • mitochondrial function
  • cytokine production
  • immune response

Aging research is still in the early stages, but the pace of discovery has quickened.  I will update this guide to the science of skin aging as new discoveries are found.  But at this time, don;t waste money on skin care that claism to target the genes that cause skin aging.  It is too early for us to completely understand what genes to target with antiaging skin care.

How Inflammation Causes Skin Aging

When skin gets inflamed, many destructive pathways get turns on known as inflammaging. Free radicals, destructive enzymes like matrix metalloproteinases, and immune cells all cause skin damage in inflamed skin that leads to aging.  Build up of senescent cells also occurs.  To prevent skin aging it is important to identify and remove the causes of skin inflammation and to turn off inflammation with anti-inflammatory skincare ingredients.

Using the wrong skin care products can cause skin inflammation.

Cosmeceutical Antiaging Skincare Ingredients Should Target the Causes of Skin Aging

Retinoids, growth factors, exosomes, defensins, antioxidants, heparan sulfate and ascorbic acid are all antiaging ingredients used to target the causes of aging skin.

 The causes of skin aging are complicated.  The best way for you to choose antiaging skincare that is right for you is to shop using your Baumann Skin Type.

level up your skincare knowledge

References:

 

[1] Baumann L. Ch 39 Antioxidants in Baumann’s Cosmetic Dermatology (McGraw Hill 2022)

[2] Werninghaus K: The role of antioxidants in reducing photodamage, in Photodamage, edited by B Gilchrest. London, Blackwell Science Inc., 1995, p 249.

[3] Dhar A, Young MR, Colburn NH: The role of AP-1, NF-kappaB and ROS/NOS in skin carcinogenesis: the JB6 model is predictive. Mol Cell Biochem. 234–235:185, 2002.

[4] Fisher GJ, Wang ZQ, Datta SC et al: Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med. 337:1419, 1997.

[5] Lopez-Otin, C., Blasco, M.A., Partridge, L., Serrano, M., Kroemer, G., 2013. The hallmarks

of aging. Cell 153, 1194–1217.

[6] Levine, B., and Kroemer, G. (2019). Biological functions of autophagy genes: a disease perspective. Cell 176, 11–42.

[7] G. Nelson, J. Wordsworth, C. Wang, D. Jurk, C. Lawless, C. Martin-Ruiz, et al. A senescent cell bystander effect: senescence-induced senescence Aging Cell, 11 (2012), pp. 345-349

[8] J.F. Passos, G. Saretzki, S. Ahmed, G. Nelson, T. Richter, H. Peters, etal. Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence

PLoS Biol, 5 (2007), p. e110

[9] C. Franceschi, J. Campisi Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases, Gerontol. A Biol. Sci. Med. Sci., 69 (Suppl. 1) (2014), pp. S4-9

[10] Morselli E, Maiuri MC, Markaki M, Megalou E, Pasparaki A, Palikaras K, Criollo A, Galluzzi L, Malik SA, Vitale I, Michaud M, Madeo F, Tavernarakis N, Kroemer G. Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis. 2010

[11] Morselli E, Maiuri MC, Markaki M, Megalou E, Pasparaki A, Palikaras K, Criollo A, Galluzzi L, Malik SA, Vitale I, Michaud M, Madeo F, Tavernarakis N, Kroemer G. Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis. 2010

[12] Lee, J. H., Moon, J. H., Nazim, U. M., Lee, Y. J., Seol, J. W., Eo, S. K., ... & Park, S. Y. (2016). Melatonin protects skin keratinocyte from hydrogen peroxide-mediated cell death via the SIRT1 pathway. Oncotarget, 7(11), 12075.

[13] Tigges, J., Krutmann, J., Fritsche, E., Haendeler, J., Schaal, H., Fischer, J. W., ... & Ventura, N. (2014). The hallmarks of fibroblast ageing. Mechanisms of ageing and development138, 26-44.

[14] Glass D, Viñuela A, Davies MN, Ramasamy A, Parts L, Knowles D, Brown AA, Hedman AK, Small KS, Buil A, Grundberg E, Nica AC, Di Meglio P, et al., and MuTHER consortium. Gene expression changes with age in skin, adipose tissue, blood and brain. Genome Biol. 2013; 14:R75.

[15] Baumann L. Intrinsic Aging Ch. 5 in Baumann’s Cosmetic Dermatology (McGraw Hill 2022)

[16] Kimball AB, Alora-Palli MB, Tamura M, Mullins LA, Soh C, Binder RL, Houston NA, Conley ED, Tung JY, Annunziata NE, Bascom CC, Isfort RJ, Jarrold BB, et al.. Age-induced and photoinduced changes in gene expression profiles in facial skin of Caucasian females across 6 decades of age. J Am Acad Dermatol. 2018; 78:29–39

[17] McGrath, J. A., Robinson, M. K., & Binder, R. L. (2012). Skin differences based on age and chronicity of ultraviolet exposure: results from a gene expression profiling study. British Journal of Dermatology166, 9-15.

 

 

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