The life history of man is summarized as a birth-aging-disease-death. Man eventually ages and dies. How long can humans live? What is aging? Why do we age? Is aging inevitable? Can we rejuvenate? Recent researches on biological aging suggest that humans might overcome aging and rejuvenate. In this paper, we review the biologic characteristics of aging and the latest results of biological aging research, implicating that aging can be controlled, further treated, and that humans can ultimately be rejuvenated.
Aging* ; Cell Aging ; Humans ; Population Characteristics ; Rejuvenation

The life history of man is summarized as a birth-aging-disease-death. Man eventually ages and dies. How long can humans live? What is aging? Why do we age? Is aging inevitable? Can we rejuvenate? Recent researches on biological aging suggest that humans might overcome aging and rejuvenate. In this paper, we review the biologic characteristics of aging and the latest results of biological aging research, implicating that aging can be controlled, further treated, and that humans can ultimately be rejuvenated.
Aging ; Cell Aging ; Humans ; Population Characteristics ; Rejuvenation

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by SA-β-gal staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.
Autophagy ; Cell Aging* ; Fibroblasts ; Humans ; Skin ; Skin Aging

No abstract available.
Aging* ; Cell Aging ; DNA* ; Oligonucleotide Array Sequence Analysis*

As a major component of the epidermal tissue, a primary keratinocyte has served as an essential tool not only for the study of pathogenesis of skin-related diseases but also for the assessment of potential toxicities of various chemicals used in cosmetics. However, its short lifespan in ex vivo setting has been a great hurdle for many practical applications. Therefore, a number of immortalization attempts have been made with success to overcome this limitation. In order to understand the immortalization process of a primary keratinocyte, several key biological phenomena governing its lifespan will be reviewed first. Then, various immortalization methods for the establishment of stable keratinocyte cell lines will be explained. Finally, its application to a three-dimensional skin culture system will be described.
Aging ; Biological Phenomena ; Cell Line ; Keratinocytes* ; Skin*

CD28 is a primary co-stimulatory receptor that is essential for successful T cell activation, proliferation, and survival. While ubiquitously expressed on naive T cells, the level of CD28 expression on memory T cells is largely dependent on the T-cell differentiation stage in humans. Expansion of circulating T cells lacking CD28 was originally considered a hallmark of age-associated immunological changes in humans, with a progressive loss of CD28 following replicative senescence with advancing age. However, an increasing body of evidence has revealed that there is a significant age-inappropriate expansion of CD4⁺CD28⁻ T cells in patients with a variety of chronic inflammatory diseases, suggesting that these cells play a role in their pathogenesis. In fact, expanded CD4⁺CD28⁻ T cells can produce large amounts of proinflammatory cytokines such as IFN-γ and TNF-α and also have cytotoxic potential, which may cause tissue damage and development of pathogenesis in many inflammatory disorders. Here we review the characteristics of CD4⁺CD28⁻ T cells as well as the recent advances highlighting the contribution of these cells to several disease conditions.
Cell Aging ; Cytokines ; Humans ; Memory ; T-Lymphocytes*

No abstract available.
Apoptosis ; Cell Aging ; Humans ; Keratinocytes ; Tretinoin

Cellular senescence is a mechanism that induces an irreversible growth arrest in all somatic cells. Senescent cells are metabolically active but lack the capacity to replicate. Evolutionary theories suggest that cellular senescence is related to the organismal decline occurring in aging organisms. Also, such theories describe senescence as an antagonistically pleiotropic process that can have beneficial or detrimental effect on the organism. Cellular senescence is believed to be involved in the cellular changes observed as aging progresses. Accumulation of senescent cells appears to occur widely as the organism ages. Furthermore, senescence is a key element of the tumor suppressor pathways. Therefore, it is part of the natural barrier against the uncontrolled proliferation observed in cellular development of malignancies in multicellular organisms. Activation of the senescence process guarantees a limited number of cellular replications. The genetic network led by p53 is responsible for activation of senescence in response to DNA damage and genomic instability that could lead to cancer. A better comprehension of the genetic networks that control the cell cycle and induce senescence is important to analyze the association of senescence to longevity and diseases related to aging. For these reasons, experimental research both in vitro and in vivo aims to develop anticancer therapies based on senescence activation. The last decade of research on role and function of senescence in aging and cancer are discussed in this paper.
Aging ; Cell Aging ; Cell Cycle ; Comprehension ; DNA Damage ; Genomic Instability ; Longevity ; Telomere

This experiment tried to elucidate the characteristics of senescence and differentiation in the reconstituted skin and the monolayer cultured human keratinocytes in vitro, respectively. While the keratinocytes were cultivated from undifferentiated state to completely senescent and differentiated, the monolayer cultured cells of every passage were doubly stained with SA-beta-gal initially, then keratins or involucrin. We also performed the SA-beta-gal enzyme staining and the immuno-reaction such as keratins or involucrin in the reconstituted skin. The results were as follows: Lack of reactivity against SA-beta-gal in the reconstituted skin indicated that there was no senescence occurred. The reconstituted skin showed decreased expression of K10 and preceded expression of involucrin compare to in vivo skin. Nevertheless, the reconstituted skin which did not express the K10 or involucrin in the basal cell maintained the differentiation system similar to that of in vivo skin. On the other hand, the monolayer cultured keratinocytes showed a thoroughly different pattern in the senescent and differentiating process. SA-beta-gal was colocalized with K10 or involucrin in the cells of high percentage ratio by the double staining method, and this indicated that the senescence and differentiation in the kratinocytes were simultaneously progressed. Reaching the nearer stage leading to the cell death, the cells choosed the one of senescence or differentiation pathway. It was supported by the fact that the percentage index of double staining together with SA-beta-gal and involucrin was lower at passage 5 than passage 1~4. The SA-beta-gal's reactivity was maximally reached at passage 4 and the involucrin maximally reached at passage 5. These trends suggested that the senescence was preceded by the differentiation. In conclusion, the reconstituted skin maintained only the differentiation system without the cell senescent process similar to the in vivo while the senescent and differentiating events were simultaneously processed in the monolayer cultured keratinocytes.
Aging ; Cell Aging* ; Cell Death ; Cells, Cultured ; Hand ; Humans* ; Keratinocytes* ; Skin*

Caveolin-1 (Cav-1) is a trans-membrane protein that is a major component of the caveolae structure on the plasma membrane. Cav-1 is involved in the regulation of various cellular processes, including cell growth, differentiation, endocytosis, and in particular it has been implied in cellular senescence. Here we review current knowledge about Cav-1 in cellular signaling and discuss the role of Cav-1 in aging-related diseases.
Caveolae ; Caveolin 1 ; Cell Aging ; Cell Membrane ; Endocytosis