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Sex hormonal regulation and hormesis in aging and longevity: role of vitagenes

  • Research Article
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Journal of Cell Communication and Signaling Aims and scope

Abstract

Aging process is accompanied by hormonal changes characterized by an imbalance between catabolic hormones, such as cortisol and thyroid hormones which remain stable and hormones with anabolic effects (testosterone, insulin like growth factor-1 (IGF-1) and dehydroepiandrosterone sulphate (DHEAS), that decrease with age. Deficiencies in multiple anabolic hormones have been shown to predict health status and longevity in older persons.

Unlike female menopause, which is accompanied by an abrupt and permanent cessation of ovarian function (both folliculogenesis and estradiol production), male aging does not result in either cessation of testosterone production nor infertility. Although the circulating serum testosterone concentration does decline with aging, in most men this decrease is small, resulting in levels that are generally within the normal range. Hormone therapy (HT) trials have caused both apprehension and confusion about the overall risks and benefits associated with HT treatment. Stress-response hormesis from a molecular genetic perspective corresponds to the induction by stressors of an adaptive, defensive response, particularly through alteration of gene expression. Increased longevity can be associated with greater resistance to a range of stressors. During aging, a gradual decline in potency of the heat shock response occur and this may prevent repair of protein damage. Conversely, thermal stress or pharmacological agents capable of inducing stress responses, by promoting increased expression of heat-shock proteins, confer protection against denaturation of proteins and restoration of proteome function. If induction of stress resistance increases life span and hormesis induces stress resistance, hormesis most likely result in increased life span. Hormesis describes an adaptive response to continuous cellular stresses, representing a phenomenon where exposure to a mild stressor confers resistance to subsequent, otherwise harmful, conditions of increased stress. This biphasic dose–response relationship, displaying low-dose stimulation and a high-dose inhibition, as adaptive response to detrimental lifestyle factors determines the extent of protection from progression to metabolic diseases such as diabetes and more in general to hormonal dysregulation and age-related pathologies. Integrated responses exist to detect and control diverse forms of stress. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of several genes termed vitagenes. Vitagenes encode for heat shock proteins (Hsps), thioredoxin and sirtuin protein systems. Nutritional antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways under control of Vitagene protein network. Here we focus on possible signaling mechanisms involved in the activation of vitagenes resulting in enhanced defense against functional defects leading to degeneration and cell death with consequent impact on longevity processes.

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Abbreviations

LOH:

Late-onset hypogonadism

CBP:

CREB-binding protein

DHEA:

Dehydroepiandrosterone

SIRT:

Sirtuin

DHEAS:

Dehydroepiandrosterone sulfate

CO:

Carbon monoxide

SHBG:

Sex hormone binding globulin

NO:

Nitric oxide

HT:

Hormone therapy

ARE:

Antioxidant response element

HSR:

Heat shock response

Nrf2:

Nuclear factor erythroid 2-related factor

Hsp:

Heat shock protein

Keap1:

Kelch ECH Associating Protein 1

HO-1:

Heme oxygenase-1

Maf:

Musculoaponeurotic fibrosarcoma

HSF:

Heat shock transcription factor

AD:

Alzheimer’s disease

HSE:

Heat shock elements

DBD:

DNA-binding domain

HR:

Hydrophobic heptad repeats

TAD:

Trans-activation domain

eEF1A:

Eukaryotic elongation factor 1A

HSR-1:

Heat shock RNA-1

MAP kinases:

MAPK

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Catania, Via Andrea Doria, 95100, Catania, Italy

    V. Calabrese, G. Koverech, A. Koverech, A. Trovato Salinaro & M. Scuto

  2. Department of Medicine and Surgery Specialties, University of Catania, Catania, Italy

    C. De Pasquale

  3. Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy

    G. Scapagnini & S. Davinelli

  4. SannioTech Consortium Research Center, Apollonia (BN), Italy

    V. Calabrese & G. Scapagnini

  5. Environmental Health Sciences Division, School of Public Health, University of Massachusetts, Amherst, MA, USA

    E. J. Calabrese

  6. Division of Obstetrics and Gynaecology, University Hospitals of Pisa, Pisa, Italy

    A. R. Genazzani

Authors
  1. V. Calabrese
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  2. G. Scapagnini
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  3. S. Davinelli
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  4. G. Koverech
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  5. A. Koverech
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  6. C. De Pasquale
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  7. A. Trovato Salinaro
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  8. M. Scuto
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  9. E. J. Calabrese
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  10. A. R. Genazzani
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Correspondence to V. Calabrese.

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Calabrese, V., Scapagnini, G., Davinelli, S. et al. Sex hormonal regulation and hormesis in aging and longevity: role of vitagenes. J. Cell Commun. Signal. 8, 369–384 (2014). https://doi.org/10.1007/s12079-014-0253-7

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  • DOI: https://doi.org/10.1007/s12079-014-0253-7

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