With 2012 being the European Year for Active Aging, many initiatives are drawing public awareness to the importance of aging research (gerontology). Aging research is interdisciplinary as it concerns many different fields such as biology, medicine, social sciences, product design and technologies, as well as demography. Biogerontology aims at understanding the biological mechanisms of molecular, cellular, organ, and organismic aging. Current concepts of aging, in particular aging in higher organisms such as mammals, perceive cellular senescence as a key process contributing to aging of tissues and the entire organism. Starting from the initial observation by Leonard Hayflick that normal human cells have a limited replicative capacity [1], in the last 5 decades molecular mechanisms driving cellular senescence have been established, based primarily on experiments with cultured cells. Senescent cells have been identified in vivo in mammalian tissues, including tissues from mice, non-human primates, and humans. However, the mechanisms underlying cellular senescence in vivo and the functional significance of senescent cells are poorly understood. The clearance of age-associated damage plays an important role in determining lifespan. This is particularly well documented for molecular damage at the subcellular level, including repair of nucleic acids, repair of certain protein modifications, and the turnover of damaged proteins. In addition, recent data suggest that clearance of damaged organelles by autophagy is another mechanism assuring longevity [2]. There is good evidence linking repair mechanisms, for example DNA repair, to lifespan regulation in many species including humans, as best exemplified by premature aging syndromes such as Werner syndrome caused by mutations of DNA repair enzymes [3]. Much less is known about mechanisms that control the abundance of senescent cells in mammalian tissues; in particular, mechanisms by which damaged cells are removed are poorly understood. According to recent evidence, the clearance of p16Ink4a-positive senescent cells delays aging-associated disorders in mice indicating that cellular senescence is causally implicated in generating age-related phenotypes, and that removal of senescent cells can prevent or delay tissue dysfunction and extend health span [4]. There is also evidence that components of the innate immune system contribute to the clearance of senescent cells in certain human tissues [5]; however, the significance of innate and adaptive immune responses for the clearance of senescent or damaged cells in aging tissues remains to be investigated. Interestingly, the immune system itself is strongly affected by the aging process, as the involution of the thymus starts early in life and is nearly complete between the age of 40 and 50 (fig. (fig.1)1) [6]. With thymic involution, the output of naive T cells decreases, and antigen-experienced cells – senescent cells among them – accumulate. Senescent T cells have an effector phenotype and have been shown to be pro-inflammatory and cytotoxic. They have short telomeres and do not proliferate well [7]. Due to a decreased DNA damage response, they are sensitized to apoptotic cell death [8]. They can still survive in the presence of IL-15, a cytokine which is produced in large amounts by the aged bone marrow [9, 10]. IL-15 as well as IFN-γ have also been discussed as suppressors of erythropoiesis [11]. It seems possible that low erythropoiesis in old age may at least in part be explained by the overproduction of both cytokines in the bone marrow niche. Fig. 1 Aging of the immune system. A Thymic involution. B Modified from Immunol Today 17, George AJ and Ritter MA, Thymic involution with aging: obsolescence or good housekeeping?, pp. 267–272, 1996, with permission of Elsevier.' As biological aging is known to represent a predisposing factor for the development and progression of age-related diseases [12, 13], it seems of utmost importance to find intervention strategies to prevent or at least postpone aging and its pathological consequences. A key mechanism of postponing age-associated damage is caloric restriction which has been shown to extend the lifespan in rodents and the healthspan in non-human primates [14]. Effects of caloric restriction on human health are well documented; however, so far it is not clear whether caloric restriction has the potential to extend human lifespan. Although caloric restriction is a well accepted paradigm with regard to extending lifespan, molecular mechanisms by which caloric restriction contributes to lifespan extension are not completely understood. There are reports from lower eukaryotic model organisms suggesting the involvement of various distinct pathways in lifespan extension by caloric restriction; however, this question is not resolved for any mammalian system. In the past, many attempts have been made to extend lifespan and healthspan by pharmacological and/or nutritional interventions. Based on the assumptions of the ‘Free Radical Theory of Aging’, large projects on supplementation of antioxidants were conducted; however, no beneficial effects of general antioxidant supplementation on age-associated diseases could be observed [15]. In addition, there is emerging evidence that reactive oxygen species can trigger beneficial signaling responses that prolong lifespan. More recently, small molecule-based interventions have been developed with the aim to extend lifespan/healthspan by targeting molecular pathways known to contribute to longevity. In this respect, lifespan extension by several of these treatments was reported in model organisms up to the level of fruit flies. One of these compounds, resveratrol, which is believed to target and activate sirtuins, was shown in long-term experiments in mice to improve health parameters under high-calorie diet conditions, but had no effect on lifespan under standard conditions [16]. More recently, feeding of mice with rapamycin, an antagonist of the TOR pathway, was shown to extend lifespan [17]. Furthermore, another paradigm was established based on the observation that feeding model organisms with spermidine increases lifespan through elevating the rate of autophagy [2]. The described measures and therapeutic approaches will hopefully enable as many people as possible to grow old in good health. Considering the demographic changes presently taking place in the whole of Europe, one realizes that it is not only a desirable goal for individuals to stay independent and mobile as long as possible, but that it is becoming increasingly important to relieve society of the enormous economic burden of age-related diseases, hospitalization, and long-term care.