The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates

Abstract

Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs) and geriatric syndromes (GSs), is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic biological mechanisms. A consequence is that the primary target of medicine is to combat aging instead of any single ARD/GSs one by one, as favored by the fragmentation into hundreds of specialties and sub-specialties. If the same molecular and cellular mechanisms underpin both aging and ARDs/GSs, a major question emerges: which is the difference, if any, between aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed by analyzing in particular frailty, sarcopenia, chronic obstructive pulmonary disease, cancer, neurodegenerative diseases such as Alzheimer and Parkinson as well as Down syndrome as an example of progeroid syndrome. According to this integrated view, aging and ARDs/GSs become part of a continuum where precise boundaries do not exist and the two extremes are represented by centenarians, who largely avoided or postponed most ARDs/GSs and are characterized by decelerated aging, and patients who suffered one or more severe ARDs in their 60s, 70s, and 80s and show signs of accelerated aging, respectively. In between these two extremes, there is a continuum of intermediate trajectories representing a sort of gray area. Thus, clinically different, classical ARDs/GSs are, indeed, the result of peculiar combinations of alterations regarding the same, limited set of basic mechanisms shared with the aging process. Whether an individual will follow a trajectory of accelerated or decelerated aging will depend on his/her genetic background interacting lifelong with environmental and lifestyle factors. If ARDs and GSs are manifestations of accelerated aging, it is urgent to identify markers capable of distinguishing between biological and chronological age to identify subjects at higher risk of developing ARDs and GSs. To this aim, we propose the use of DNA methylation, N-glycans profiling, and gut microbiota composition to complement the available disease-specific markers.

Undulating changes in human plasma proteome across lifespan are linked to disease

“…4h-i). The fact that the proteome defining these two diseases also changed in old individuals of a separate disease-free cohort supports the notion of accelerated aging in DS and AD 32,33 . Altogether, these results show that the waves of proteomic aging are differentially linked to the genomic and proteomic traits of various diseases.…”

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

“…Age-related degenerative diseases, however, share several physiopathologic pathways,93 so that a role of gut microbiota in the development and clinical course of AD is highly plausible, even if not yet comprehensively investigated. In fact, studies exploring the possible contribution of infective agents in AD onset have mainly focused on the central nervous system or systemic infections, but not on microbiota 94.…”

Neuroimaging Studies Illustrate the Commonalities Between Ageing and Brain Diseases

“…As mentioned, these phenomena have also been associated with neurobiology of normal ageing . The neurobiological overlap between ageing and disease is paralleled outside the brain, with mechanistic commonalities observed in other bodily systems (see Franceschi and colleagues for review) …”