Fight Aging!

Animal study data makes it very clear that senescent cells are actively involved in producing the age-related dysfunction that leads to disease and mortality. Senescent cells grow in number with age and generate signaling, the senescence-associated secretory phenotype, that disrupts tissue structure and function. Selectively destroying senescent cells via the use of senolytic therapies removes this influence to produce a profound and rapid reversal of many measurable aspects of aging in mice. Some of these therapies are used by a growing number of patients with access to anti-aging physicians, and human trials have taken place to produce promising early results. Nonetheless we are still some way from a good enough understanding of dosing in humans and enough rigorous human data to convince the world that this is as impressive as it appears to be in the laboratory.

Clearance of senescent cells should help to, at the very least, slow the progression towards neurodegenerative conditions, such as the prevalent mild cognitive impairment in older individuals. In today's open access materials, researchers report on the ability to correlate circulating markers of the burden of senescent cells with the risk of mild cognitive impairment. Beyond the point that more ways to assess the risk of neurodegeneration improve the ability to prevent such conditions via early intervention, this adds to the body of evidence to suggest that presently available senolytic therapies with a good safety profile, such as intermittent treatment with the dasatinib and quercetin combination, should be widely used as preventative medicine in the older population.

Plasma senescence associated secretory proteins: A new link to mild cognitive impairment

Cellular senescence is widely acknowledged hallmark of aging that has been implicated in the progression of several age associated disorders. The secretome of senescent cells, termed as senescence associated secretory phenotype (SASP), consists of a number of inflammatory cytokines as well as growth factors and proteases that can lead to paracrine disruption of normal tissue structure and function and propagate senescence in neighboring cells. Moreover, many SASP molecules have been identified as potential biomarkers of aging and associated traits. In cases of age associated neurodegenerative diseases that can lead to dementia or cognitive impairment, increased senescence has been observed in multiple cell types in brain.

Mild cognitive impairment (MCI) is defined as a condition defined by cognitive impairment with minimal impairment of daily activities. It is observed in about 10-20% of individuals over 65 years of age and about 10% of individuals with MCI can progress to dementia every year. There are few potential plasma biomarkers that have been reported, particularly senescence-associated protein biomarkers. Therefore, there is a need to identify new robust potential plasma biomarkers that can be applied clinically for diagnosis of MCI.

A new study explored the connection between cellular senescence and MCI by analyzing the plasma levels of certain SASP markers to predict risk of MCI among older adults. The study is based on the data from the Lifestyle Interventions for Elders (LIFE), a large cohort study designed to assess the effects of physical activity and health education on mobility in sedentary older adults. The authors assessed a panel of 27 SASPs that were previously identified as markers associated with mobility disability. Among these, higher plasma levels of myeloperoxidase (MPO) and Membrane metalloprotease-7 (MMP7) and reduced levels of MMP1 reportedly led to increased risk of MCI in older adults. Importantly, MPO and MMP7 were longitudinally associated with future MCI (24 months later), underscoring their predictive potential. These markers had been previously reported to be associated with different neurological disorders including Alzheimer's disease. However, the current study points to a potential mechanistic connection with cellular senescence and SASP as players in development of MCI. If certain cases of MCI are driven by cellular senescence, a possibility that needs to be further explored, then senotherapeutic interventions may offer a novel therapeutic opportunity.