Frailty
Disease7 papers17 findings
Human studies associate frailty with lower handgrip strength in males, depression in females and GDF-15. A human trial reports reduced frailty with aerobic exercise during daycare rehabilitation; reviews link frailty to functional decline and describe reduced frailty with renal rehabilitation during maintenance haemodialysis.
- Human trial1
- Humans3
Interventions
2Aerobic exercise
downin humans1Very low certainty
1 study
Aerobic exercise
downin humans1Very low certainty
Aerobic exercise decreases frailty in humans.
Human trialduring daycare rehabilitationseated stepping and arm movements at 120 bpm for two 2-minute setstwo 2-minute sets6 monthsn = 252
Effect of seated aerobic exercise on physical endurance in long-term care recipients: secondary analysis of a cluster non-randomized controlled trial · The Journal of frailty & aging · 4 Sep 2026
Renal rehabilitation
downin humans1Low certainty
1 study
Renal rehabilitation
downin humans1Low certainty
Renal rehabilitation decreases frailty in humans.
Reviewmaintenance hemodialysis
Renal Rehabilitation and Its Relationship with Anemia, Nutritional Status, and Activities of Daily Living in Patients Undergoing Maintenance Hemodialysis: A Systematic Review · Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia · 31 Aug 2026
Effects
3Cognitive function
downin humans1
1 study
Cognitive function
downin humans1
Frailty impairs cognitive function in humans.
Humansin late-life depression patients
Relationship between cognitive function and brain activation in late-life depression patients with and without frailty: a functional near-infrared spectroscopy study · Journal of affective disorders · 28 Aug 2026
Bone mineral density
downin mice1
1 study
Bone mineral density
downin mice1
Frailty decreases bone mineral density in mice.
“BMD was similar between Prefrail and Frail, while both differed from Robust, suggesting that BMD loss occurred early in the progression to frailty.”
Animalsin prefrail and frail compared to robust micebonefemales
PROGRESSION TO FRAILTY – THE ROLE OF MUSCLE RESILIENCE · GSA 2024 abstract · 31 Dec 2024
Tetanic force
downin mice1
1 study
Tetanic force
downin mice1
Frailty decreases tetanic force in mice.
“Tetanic force (soleus) in Frail mice was significantly reduced compared to Prefrail and Robust mice.”
Animalsin frail compared to prefrail and robust micesoleusfemales
PROGRESSION TO FRAILTY – THE ROLE OF MUSCLE RESILIENCE · GSA 2024 abstract · 31 Dec 2024
Associations
11Depression
upin humans2
2 studies
Depression
upin humans2
Depression raises the risk of frailty in humans.
Review
Risk factors for frailty in aging: from sex and gender and genetic determinants to the exposome · Journal of toxicology and environmental health. Part B, Critical reviews · 6 Sep 2026
Depression is associated with frailty in humans (B = 0.306, p = 0.011).
Humansmultivariable linear regressionfemales
Health dimensions and sex differences in frailty among nursing home residents: a cross-sectional study in Bilbao, Spain · Annals of geriatric medicine and research · 3 Sep 2026
Functional decline
upin humans1
1 study
Functional decline
upin humans1
Frailty raises the risk of functional decline in humans.
Review
Screening for "Frailty – Sarcopenia – Nutrition - Physical activity" among older population in Henan province, China: a study protocol of a prospective, observational cohort study · Research Square · 25 Sep 2026 · Preprint
GDF-15
upin humans1
1 study
GDF-15
upin humans1
GDF-15 is associated with frailty in humans.
Humansintermediate tertile compared with lowest tertile2-year follow-upn = 206
Association of plasma growth differentiation factor-15 with the frailty phenotype - Evidence from the COGFRAIL study · The Journal of frailty & aging · 4 Sep 2026
Handgrip strength
downin humans1
1 study
Handgrip strength
downin humans1
Handgrip strength is associated with frailty in humans (B = -0.066, p = 0.041).
Humansmultivariable linear regressionmales
Health dimensions and sex differences in frailty among nursing home residents: a cross-sectional study in Bilbao, Spain · Annals of geriatric medicine and research · 3 Sep 2026
Cortical activation
downin humans1
1 study
Cortical activation
downin humans1
Frailty is associated with cortical activation in humans.
Humansduring a verbal fluency task in late-life depression patients
Relationship between cognitive function and brain activation in late-life depression patients with and without frailty: a functional near-infrared spectroscopy study · Journal of affective disorders · 28 Aug 2026
Vitamin D3 + omega-3 fatty acids + exercise
downin humans1High certainty
1 study
Vitamin D3 + omega-3 fatty acids + exercise
downin humans1High certainty
Vitamin D3 + omega-3 fatty acids + exercise lowers the risk of frailty in humans.
“Notably, the combined supplementation of vitamin D3, omega-3s, and a structured exercise program reduced the risk of becoming pre-frail.”
Reviewpre-frail
Few Pharmacologic Interventions Prevent or Mitigate Frailty: A Systematic Review · GSA 2025 abstract · 31 Dec 2025
TNF-alpha
upin humans1OR 1.21
1 study
TNF-alpha
upin humans1OR 1.21
TNF-alpha is associated with frailty in humans (OR = 1.21, 95% CI 1.07–1.36).
“Elevated IL-6 (OR = 1.14, 1.01–1.30) and TNF-α (OR = 1.21, 1.07–1.36) correlated with frailty.”
Humansserum
The Association between Frailty and Inflammatory Biomarkers in the Elderly · GSA 2025 abstract · 31 Dec 2025
IL-6
upin humans1OR 1.14
1 study
IL-6
upin humans1OR 1.14
IL-6 is associated with frailty in humans (OR = 1.14, 95% CI 1.01–1.30).
“Elevated IL-6 (OR = 1.14, 1.01–1.30) and TNF-α (OR = 1.21, 1.07–1.36) correlated with frailty.”
Humansserum
The Association between Frailty and Inflammatory Biomarkers in the Elderly · GSA 2025 abstract · 31 Dec 2025
Hemoglobin-to-red cell distribution width ratio
downin humans1OR 0.13
1 study
Hemoglobin-to-red cell distribution width ratio
downin humans1OR 0.13
Hemoglobin-to-red cell distribution width ratio is associated with frailty in humans (OR = 0.13, 95% CI 0.03–0.44).
“Adjusted analyses identified NLR (OR = 1.57, 95%CI=1.07–2.30), dNLR (OR = 1.59, 1.11–2.27), and HRR (OR = 0.13, 0.03–0.44) as independent frailty predictors.”
Humansadjusted analysesblood
The Association between Frailty and Inflammatory Biomarkers in the Elderly · GSA 2025 abstract · 31 Dec 2025
Derived neutrophil-to-lymphocyte ratio
upin humans1OR 1.59
1 study
Derived neutrophil-to-lymphocyte ratio
upin humans1OR 1.59
Derived neutrophil-to-lymphocyte ratio is associated with frailty in humans (OR = 1.59, 95% CI 1.11–2.27).
“Adjusted analyses identified NLR (OR = 1.57, 95%CI=1.07–2.30), dNLR (OR = 1.59, 1.11–2.27), and HRR (OR = 0.13, 0.03–0.44) as independent frailty predictors.”
Humansadjusted analysesblood
The Association between Frailty and Inflammatory Biomarkers in the Elderly · GSA 2025 abstract · 31 Dec 2025
All 11Fewer
Neutrophil-to-lymphocyte ratio
upin humans1OR 1.57
1 study
Neutrophil-to-lymphocyte ratio
upin humans1OR 1.57
Neutrophil-to-lymphocyte ratio is associated with frailty in humans (OR = 1.57, 95%CI=1.07–2.30).
“Adjusted analyses identified NLR (OR = 1.57, 95%CI=1.07–2.30), dNLR (OR = 1.59, 1.11–2.27), and HRR (OR = 0.13, 0.03–0.44) as independent frailty predictors.”
Humansadjusted analysesblood
The Association between Frailty and Inflammatory Biomarkers in the Elderly · GSA 2025 abstract · 31 Dec 2025
Trial sponsors
Company1 trialPhase 1/265 people
Company1 trialPhase 1/212 people
Company1 trial26 people
2 trialsPhase 4248 people
Donaghue Medical Research Foundation
1 trialPhase 4150 people
Washington University School of Medicine
1 trialPhase 3129 people
VA Office of Research and Development
1 trialPhase 3114 people
2 trialsPhase 2154 people
Funding
National Institute on AgingUS$15mNational Cancer InstituteUS$2.1mNational Heart, Lung, and Blood InstituteUS$1.3m36 grants since 2014
Frailty and Influenza Vaccination Among Older Adults
Veterans AffairsVA Greater Los Angeles Healthcare System2024–2029
Lifestyle Intervention plus Metformin to Treat Frailty in Older Veterans with Obesity
Veterans AffairsMichael E. DeBakey VA Medical Center2020–2026
Frailty and Resiliency in Older Adults with Acute Myocardial Infarction
National Heart, Lung, and Blood InstituteCleveland Clinic Lerner Com-cwruUS$182.5k2020–2027
XFIT: An Exercise-based Frailty Intervention in Lung Transplant Candidates
National Heart, Lung, and Blood InstituteUniversity of California, San FranciscoUS$776.8k2024–2029
National Cancer InstituteUniversity of Maryland BaltimoreUS$638.5k2026–2031
National Institute on AgingVanderbilt University Medical CenterUS$75.6k2025–2030
Machine learning based frailty index for the genetically diverse mice
National Institute on AgingThe Jackson LaboratoryUS$667.3k2022–2027
Skin immunity as a function of frailty, aging, and skin microbiome composition
National Institute on AgingDuke UniversityUS$446.7k2024–2029
National Institute of Diabetes and Digestive and Kidney DiseasesUniversity of California, San FranciscoUS$702.2k2023–2028
National Institute on AgingCedars-Sinai Medical CenterUS$1.5m2025–2030
Latest
773Longer chains in lipids were linked to aging in humans
An analysis of human lipids, molecules used in cell membranes, linked aging to longer fatty-acid chains and lower levels of shorter lipids.An analysis of human lipids, molecules used in cell membranes, linked aging to longer fatty-acid chains and lower levels of shorter lipids.
Model predicted frailty risk in older emergency patients
The model achieved a discrimination score of 0.940 in 143 patients set aside for testing, in a retrospective study of older emergency patients.The model achieved a discrimination score of 0.940 in 143 patients set aside for testing, in a retrospective study of older emergency patients.
DNA damage differed by sex in mice with impaired DNA repair
Experiments in mice with impaired DNA repair identified a female-specific metabolic pathway; a dietary supplement restored muscle force and metabolic…Experiments in mice with impaired DNA repair identified a female-specific metabolic pathway; a dietary supplement restored muscle force and metabolic profiles in females.
Biological aging and frailty linked to thinner central retinas
Blood metabolic profiles statistically accounted for 81.14% of the link with one biological age measure, compared with 19.92% for another and 32.27%…Blood metabolic profiles statistically accounted for 81.14% of the link with one biological age measure, compared with 19.92% for another and 32.27% for frailty.
Planetary Health Diet tied to lower frailty odds in older Spaniards
Across both cohorts, the odds ratio for frailty was 0.52 when comparing Spanish older adults in the highest versus lowest third of diet scores.Across both cohorts, the odds ratio for frailty was 0.52 when comparing Spanish older adults in the highest versus lowest third of diet scores.