RICERCA - BIOGERONTOLOGY

BIOGERONTOLOGY

Aging is a physiological, multifactorial process characterized by a progressive loss of function, leading to increased risk of morbidity and mortality.

Despite human life expectancy has significantly increased, the extension of the health span remains an open issue as well as the main goal of the gerontologic/geriatric research
In the last decades, the so called “hallmarks of aging” - genetic pathways and biochemical processes conserved in evolution - have been defined (i.e., genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication). The more complete understanding of the mechanisms underlying these phenomena is the start point to prevent, or at least slow down, the onset of age-related syndromes and diseases (e.g. frailty, cancer, diabetes, cardiovascular disorders, dementia)
IRCCS INRCA fosters research programs to identify molecular targets and validate innovative therapeutic approaches and multisystemic preventive interventions in preclinical settings to promote healthy, active aging. The combined use of in silico, in vitro, in vivo and ex vivo techniques guarantees results robustness and reliable transfer of novel “tools” to clinicians

López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217

CELLULAR SENESCENCE

Cellular senescence is a mechanism of response to oxidative, replicative, oncogenic and other types of stress. It has a fundamental physiological role in tumour protection and tissue regeneration. However, it is also one of the best-known hallmarks of aging because the excessive accumulation of senescent cells occurring with time converts the original physiological role into a pathological one. Thanks to the use of preclinical models especially, in which it is possible to selectively eliminate the excessive accumulation of senescent cells, it has been shown that such removal can be beneficial in atherosclerosis, sarcopenia, osteoporosis, arthrosis, reduction of recurrences after chemotherapy and many other pathological conditions associated with aging such as frailty. This knowledge has opened the perspective of being able to intervene simultaneously in many conditions of the elderly using drugs capable of selectively removing senescent cells.
IRCCS INRCA is currently involved in national and international collaborations to evaluate the discovery of new senolytics, and the efficacy of innovative genetic senolytics and of supplements containing senolytics or senotherapeutics of natural origin

GENETICS AND EPIGENETICS OF AGING

The genetic background we inherit from our parents (e.g., specific polymorphisms or alleles) and the epigenetic changes it undergoes because of internal and external stimuli (e.g., DNA methylation, histone modification, transcriptional regulation by microRNA) deeply influence our aging trajectory. The genotype is fixed, but the epigenetic profile is not. Thus, the identification of the pathways linking the epigenetic pattern and life span can support the implementation of ad hoc experimental protocols acting not on longevity per se but on health and wellbeing
IRCCS INRCA is committed to analyse the involvement of epigenetic changes in the onset and progression of various age-related diseases (e.g., cancer and cardiovascular disorders) as well as the possible, protective role of a healthy lifestyle (e.g., physical exercise, nutrition, cognitively stimulating leisure activities)

AGING AND AGE-RELATED DISEASE BIOMARKERS

A biomarker is a molecule easy to assay (no time- and cost-consuming), detectable in a biological matrix that can be sampled in a non-invasive way, able to mirror the changes of an organ or a system. Such molecules are pivotal targets for both aging and age-related diseases research. Indeed, chronological and biological aging do not overlap: the discovery of one or more biomarkers able to define biological aging is considered one of the most important breakthroughs in the gerontological field. Likewise, diagnostic, prognostic and therapies follow-up biomarkers can significantly improve the geriatric patient management and promote a more individually tailored medicine
IRCCS INRCA has been developing protocols to test the suitability of blood/urine/faeces cells, enzymes, microRNA, neurotrophins, hormones in several clinical settings (e.g., dementia, cardiovascular disorders, chronic kidney disease) and in models of biological aging (e.g., to define the person’s life expectancy)

PUBLICATIONS

	Di Palma, M., Catalano, M., Serpe, C., De Luca, M., Monaco, L., Kunzelmann, K., ... & Fattorini, G. (2023). Lipopolysaccharide augments microglial GABA uptake by increasing GABA transporter-1 trafficking and bestrophin-1 expression. Glia, 71(11), 2527-2540.
	Marcozzi, S., Bigossi, G., Giuliani, M. E., Lai, G., Giacconi, R., Piacenza, F., & Malavolta, M. (2023). Spreading Senescent Cells’ Burden and Emerging Therapeutic Targets for Frailty. Cells, 12(18), 2287.
	Bronte, G., Conteduca, V., Landriscina, M., & Procopio, A. D. (2023). Circulating myeloid-derived suppressor cells and survival in prostate cancer patients: systematic review and meta-analysis. Prostate cancer and prostatic diseases, 26(1), 41–46. https://doi.org/10.1038/s41391-022-00615-5
	Olivieri, F., Prattichizzo, F., Lattanzio, F., Bonfigli, A. R., & Spazzafumo, L. (2023). Antifragility and antiinflammaging: Can they play a role for a healthy longevity?. Ageing research reviews, 84, 101836. https://doi.org/10.1016/j.arr.2022.101836
	Conti, F., & Pietrobon, D. (2023). Astrocytic Glutamate Transporters and Migraine. Neurochemical research, 48(4), 1167–1179. https://doi.org/10.1007/s11064-022-03849-w

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BIOGERONTOLOGY

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GENETICS AND EPIGENETICS OF AGING

AGING AND AGE-RELATED DISEASE BIOMARKERS

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