Ageing Research Reviews 11 (2012) 10–31 Contents lists available at SciVerse ScienceDirect Ageing Research Reviews jo u r n al hom epage: www.elsevier.com/locate/arr Review Morphological and biochemical studies on aging and autophagy Rita Rezzani ∗ , Alessandra Stacchiotti, Luigi Fabrizio Rodella Anatomy Section, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy a r t i c l e i n f o Article history: Received 14 July 2011 Received in revised form 5 September 2011 Accepted 8 September 2011 Available online 16 September 2011 Keywords: Autophagy Aging Morphological markers Biochemical markers a b s t r a c t To maintain health in the elderly is a crucial objective for modern medicine that involves both basic and clinical researches. Autophagy is a fundamental auto-cannibalizing process that preserves cellular homeostasis and, if altered, either by excess or defect, greatly changes cell fate and can result in incapaci- tating human diseases. Efficient autophagy may prolong lifespan, but unfortunately this process becomes less efficient with age. The present review is focused on the close relationship between autophagy and age-related disorders in different tissues/organs and in transgenic animal models. In particular, it comments on the up to date liter- ature on mechanisms responsible for age-related impairment of autophagy. Moreover, before discussing about these mechanisms, it is necessary to describe the metabolic autophagic regulation of autophagy and the proteins involved in this process. At the end, these data would summarize the autophagic link with aging process, as important tools in the future biogerontology scenario. © 2011 Elsevier B.V. All rights reserved. 1. Introduction One of the major challenges in the 21st century is the aging of the population and the associated medical social and economic implications. Life expectancy exceeds 80 years in several devel- oped countries and is projected to continue to increase during the next half century (Kirkwood, 2008). Since the elderly people gradually increases, it becomes more important to understand the biological bases (i.e., processes and their mechanisms) of aging as well as morphological and molecular aspects underlining various age-related diseases. This knowledge may lead to future genetic and pharmacological interventions that can delay many aspects of decline occurring at advanced ages, prolonging the age of people in good health (Vellai et al., 2009). In the last two decades, the biolog- ical basis of aging shed light on many aging mysteries describing the age-related changes in organs of organisms. However, many questions are unresolved since the aging shows many aspects and causes (Rajawat et al., 2009; Troen, 2003). Aging is a process characterized by an accumulation of aberrant macromolecules and organelles during post-development period inducing a decrease of time survival and an increase of death risk (Rajawat and Bossis, 2008). During aging process there is a failure of maintenance and repair pathways and this induces the origin of age-related diseases and eventual death (Rattan, 2006). Accu- mulation of worn-out organelles and different cellular structures reduces molecular and cellular efficiency of biological processes ∗ Corresponding author. Tel.: +39 0303717483; fax: +39 0303717486. E-mail address: rezzani@med.unibs.it (R. Rezzani). that are important for organ homeostasis and survival. Since mod- ifications of biological processes are the main causes of aging or senescence, they are the final manifestations of unsuccessful homeostasis or failure of homeodynamics (Holliday, 2007). In par- ticular, it is possible to report that the lifespan of an organism is the sum of deleterious changes and maintenance mechanisms responding to the damage. In particular, it is known that the lifes- pan is determined by the balance between metabolism, which leads to the accumulation of damage (thus causing aging), and compensatory responses (Fig. 1). The changes are due to the accumulation of oxidized, misfolded, cross-linked or aggregated macromolecules that are morphologically not normal and so, they cannot properly function. Moreover, it is possible that these macro- molecules interfere with other molecules and organelles, or their aggregates compromising cellular functions sending also erroneous signals. Thus, the cells need to eliminate them for survival. It is known also that the cellular damage is related to aging-pathologies, including cancer, neurodegeneration, infection and muscle atrophy (Kirkwood, 2008; Hekimi and Guarente, 2003). Oxidation of DNA induces, for example, a single-or double strand breaks leading to possible mutation and determining cancer, and other diseases (Rubinsztein, 2006; Pinkston et al., 2006; Matheu et al., 2007). Nevertheless, the not defined or not known cellu- lar and biochemical markers of aging make useless the efforts for identifying the primary and secondary mechanisms responsible to damages. Many theories regarding aging have been proposed (Weinert and Timiras, 2003) and they have been divided in two categories (Troen, 2003): stochastic and genetic theories. The first theory considers the alterations occurring during the entire lifes- pan of cells as above reported, while the genetic theories suggest 1568-1637/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.arr.2011.09.001