A study led by the INCLIVA Health Research Institute at the University Clinical Hospital of Valencia provides evidence that biological aging and frailty are not inevitable processes, but rather potentially modifiable through well-designed lifestyle interventions.

The main objective of the research, whose results have just been published in Aging Cell, was to evaluate whether an intervention based on supervised physical exercise and nutritional supplementation can reverse frailty and slow biological aging, defined as the set of molecular and functional changes that reflect how the body actually ages, regardless of actual age.

Frailty is a geriatric syndrome associated with a diminished capacity to respond and high vulnerability to stressors in older adults, resulting in greater dependence and a reduced quality of life. If left unprevented or untreated, this increases the risk of disability, hospitalization, and death. Physical frailty is defined by the presence of three of five characteristics: muscle weakness, slow gait, low physical activity, exhaustion (or fatigue), and unintentional weight loss.

The starting point of this research is that frailty is a reversible condition and represents an intermediate phase between healthy aging and disability. However, there is currently a lack of biological markers that would allow for the early detection of cellular and molecular changes associated with this process or the evaluation of the actual effectiveness of interventions aimed at reversing frailty.

“This study stands out for evaluating a safe, personalized, non-pharmacological intervention in frail older adults, integrating, for the first time in a real-world clinical setting, functional improvements with biomarkers of biological aging, and demonstrating its feasibility and efficacy even during the COVID-19 pandemic. Furthermore, it provides evidence that biological aging and frailty can be modulated through healthy lifestyle habits, longitudinally integrating epigenetic clocks obtained from blood samples with functional improvements in a typically underrepresented population. These clocks, sensitive to intervention and measured using minimally invasive techniques, allow for the detection of quantifiable changes in the trajectory of biological aging in parallel with clinical improvement, opening new avenues for evaluating the real-world effectiveness of preventive programs and personalizing strategies aimed at extending autonomy and quality of life in old age,” explains Dr. María Carmen Gómez Cabrera, one of the study's principal investigators.

Supervised Physical Exercise and Nutritional Supplementation

This research evaluated the impact of a multidomain intervention based on supervised physical exercise and nutritional supplementation on frailty and biological aging in frail older adults living in the community. The study was designed as a randomized, controlled clinical trial lasting six months.
A total of 47 individuals aged 70 years and older were assigned to either an intervention or a control group. The intervention group participated in a personalized multicomponent exercise program (strength, endurance, balance, and mobility) three times per week and received a daily nutritional supplement rich in protein, vitamins, and minerals. The control group continued with usual care.

Before and after the intervention, clinical, functional, and nutritional assessments were performed, along with the analysis of molecular markers of aging from blood samples, including epigenetic clocks and an estimation of telomere length using an approach based on DNA methylation analysis. This methodology allowed for an integrated analysis of the functional and biological changes associated with the intervention.

AGING CELL