Lamin A mutations cause Hutchinson-Gilford Progeria Syndrome (HGPS), a premature aging disease. This study shows that similar nuclear defects occur in healthy aging cells, suggesting lamin A plays a role in normal aging. Old individuals' nuclei show defects like those in HGPS, including changes in histone modifications and increased DNA damage. These defects are caused by sporadic use of a cryptic splice site in lamin A, which is constitutively active in HGPS. Inhibiting this splice site reverses nuclear defects, implicating lamin A in physiological aging. HGPS is caused by a mutation in the lamin A gene (LMNA) leading to a truncated, gain-of-function lamin A isoform. HGPS cells have nuclear structural defects, including dysmorphic nuclei, increased DNA damage, and reduced nuclear proteins. Similar defects are found in old individuals, with reduced levels of markers like HP1 and Tri-Me-K9H3. These defects accumulate with age and are more pronounced in old cells. The cryptic splice site in LMNA is used sporadically in healthy individuals, leading to the production of the Δ150 LMNA mRNA and the Δ50 lamin A isoform. This isoform is present in healthy individuals and is associated with nuclear defects. Inhibiting the cryptic splice site in old cells reverses these defects, indicating that Δ50 lamin A is responsible for the nuclear abnormalities. The study shows that lamin A is involved in physiological aging, with the same molecular mechanism causing HGPS also present in aging cells. The presence of Δ50 lamin A in healthy individuals suggests it contributes to aging. Inhibiting the cryptic splice site reduces nuclear defects, indicating that lamin A is causal in age-related nuclear defects. The findings suggest that HGPS may mimic aspects of physiological aging, with lamin A playing a role in the aging process. The results highlight the importance of lamin A in maintaining nuclear structure and function during aging.Lamin A mutations cause Hutchinson-Gilford Progeria Syndrome (HGPS), a premature aging disease. This study shows that similar nuclear defects occur in healthy aging cells, suggesting lamin A plays a role in normal aging. Old individuals' nuclei show defects like those in HGPS, including changes in histone modifications and increased DNA damage. These defects are caused by sporadic use of a cryptic splice site in lamin A, which is constitutively active in HGPS. Inhibiting this splice site reverses nuclear defects, implicating lamin A in physiological aging. HGPS is caused by a mutation in the lamin A gene (LMNA) leading to a truncated, gain-of-function lamin A isoform. HGPS cells have nuclear structural defects, including dysmorphic nuclei, increased DNA damage, and reduced nuclear proteins. Similar defects are found in old individuals, with reduced levels of markers like HP1 and Tri-Me-K9H3. These defects accumulate with age and are more pronounced in old cells. The cryptic splice site in LMNA is used sporadically in healthy individuals, leading to the production of the Δ150 LMNA mRNA and the Δ50 lamin A isoform. This isoform is present in healthy individuals and is associated with nuclear defects. Inhibiting the cryptic splice site in old cells reverses these defects, indicating that Δ50 lamin A is responsible for the nuclear abnormalities. The study shows that lamin A is involved in physiological aging, with the same molecular mechanism causing HGPS also present in aging cells. The presence of Δ50 lamin A in healthy individuals suggests it contributes to aging. Inhibiting the cryptic splice site reduces nuclear defects, indicating that lamin A is causal in age-related nuclear defects. The findings suggest that HGPS may mimic aspects of physiological aging, with lamin A playing a role in the aging process. The results highlight the importance of lamin A in maintaining nuclear structure and function during aging.